Methods of treatment using topical copper ion formulations

ABSTRACT

Provided herein are topical formulations containing copper ions and methods of treating inflammatory, microbial, and arthritic conditions in various areas of the body using such formulations. Methods of treating osteoarthritis using topical copper ion treatments are provided. Methods of treating and preventing microbial infections using copper ion treatments are further provided, including methods of preventing biofilm. A topical treatment in its basic form comprises a biocompatible copper ion solution or suspension obtained by leaching of the copper ions from copper metal. The copper ion solution or suspension is combined with various carriers to form the copper ion treatment including creams, gels, lotions, foams, pastes, tampons, solutions, suppositories, body wipes, wound dressings, skin patches, and suture material. Methods of making the copper ion solution or suspension from solid copper metal in a biocompatible solution are also provided.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation-in-part and claims priority to thefollowing applications: U.S. patent application Ser. No. 13/841,882filed Mar. 15, 2013; U.S. patent application Ser. No. 13/841,992 filedMar. 15, 2013; U.S. patent application Ser. No. 13/842,310 filed Mar.15, 2013; and U.S. patent application Ser. No. 13/842,387 filed Mar. 15,2013. All patents, patent applications and publications cited herein arehereby incorporated by reference in their entirety.

FIELD OF THE DISCLOSURE

The present disclosure pertains generally to topical treatmentscontaining copper ions and to methods of treating conditions in variousanatomical areas of the body using such formulations. Some embodimentsof the present disclosure pertain to topical treatments containingcopper ions and to methods of making such topical treatments whereincopper ions from copper metal are leached into a solution. In certainembodiments, the present disclosure pertains to methods of using suchtopical formulations to treat osteoarthritis. In other embodiments, thepresent disclosure pertains to methods of preventing biofilm. Inaddition, the topical formulations have anti-fungal and anti-viralproperties.

BACKGROUND OF THE DISCLOSURE

Osteoarthritis is the most common form of arthritis, resulting fromerosion of the cartilage that normally protects the joints, leading topain, swelling and stiffness. Although osteoarthritis affects millionsof people worldwide, there is currently no cure. Current treatmentsinclude analgesics, non-steroidal anti-inflammatory drugs (NSAIDs), andsteroids. These treatments are associated with various side-effects,including gastrointestinal, cardiovascular, hematologic, hepatic andrenal damage and immune system suppression. For severely damaged joints,surgical joint replacement may become necessary. To date, topicaltreatments have been either ineffective or associated with adverseeffects. Salicylates and capsaicin were ineffective in treatingosteoarthritis, and Diclofenac sodium 1% gel (Voltaren® Gel) isassociated with adverse effects including skin rash and flu-likesymptoms. Thus, there has been an unmet medical need for effective,non-invasive treatments of osteoarthritis without significant adverseeffects.

A significant amount of human microbial infections are caused bybiofilms. Biofilms are notoriously difficult to treat, as they tend tobe less susceptible to antibiotics and host defenses than othermicrobial forms. Oral plaque is a common form of biofilm that has beenassociated with health problems, including heart attacks, mild cognitiveimpairment and dementia. A host of other medical conditions are alsocomplicated by biofilm formation, including ear infections, bacterialendocarditis, legionnaire's disease, infections associated withimplantable medical devices, lung infections associated with cysticfibrosis and hospital acquired infections.

Furthermore, many various abnormal body conditions are caused by harmfulpathogens or microbes, examples of which include bacteria, fungi andviruses. Abnormal body conditions that arise in or affect the genitalarea in women typically affect the vagina and are commonly referred toas “vaginitis”. The term “vaginitis” encompasses infection and/orinflammation of the vagina caused by bacteria, fungi and/or viruses.Vaginitis may extend to the external female genital area, i.e. thevulva, in which case it is usually referred to as “vulvovaginitis”. Inaddition, bacterial, fungal and viral conditions that affect all or partof the genital area in women. i.e. vagina, vulva and/or surroundinganatomical area, may also affect all or part of the rectal (anal) area,i.e. the rectum (anal canal) and surrounding anatomical area. In men,infection and/or inflammation of bacterial, fungal and/or viral originsmay affect all or part of the rectal area and also all or part of thegenital area, i.e. the penis, scrotum and surrounding anatomical area.

Vaginitis that is bacterial in origin is commonly called “bacterialvaginosis”. Many different bacteria are responsible for bacterialvaginosis and some of these bacteria are the cause of sexuallytransmitted diseases in women and men. Examples of sexually transmittedbacterial diseases that affect the vagina and surrounding anatomicalareas are gonorrhea and chlamydia, which appear in the generalpopulation on a widespread basis. It is estimated by the Centers forDisease Control and Prevention (CDC) that more than 700,000 peopleannually in the U.S. alone acquire new gonorrhea infections. Accordingto the CDC, over 1.3 million chlamydia infections were recorded in theU.S. in 2010 alone. In addition, there are a large number ofundiagnosed, untreated or unreported infections of gonorrhea andchlamydia because the diseases may be asymptomatic or present with onlyvery mild symptoms. Oftentimes, gonorrhea and chlamydia occur together.Gonorrhea and chlamydia may also appear in the mouth, throat and rectum(anus) in men and women. If left untreated, gonorrhea and chlamydia canspread to the uterus and/or Fallopian tubes and may cause pelvicinflammatory disease (PID), infertility, ectopic pregnancies, chronicpelvic pain and increased risk for infection with the humanimmunodeficiency virus (HIV). Untreated gonorrhea may also affect theblood, joints and heart valves. The usual treatments for gonorrhea andchlamydia are appropriate antibiotics, but history has demonstrated thatover time many bacterial diseases develop a resistance to antibiotics.Indeed, according to the CDC, numerous antibiotics previously used totreat gonorrhea have lost their effectiveness, and there is currentlyonly one remaining drug, i.e. the injectable antibiotic ceftriaxone,proven effective for treating gonorrhea. There is great concern in themedical community that it is only a matter of time before gonorrheabecomes resistant to this last remaining drug. Other types of pathogensand microbes, such as the bacteria streptococcus and staphylococcus andthe parasitic protozoan trichomonas, may also affect the vagina andsurrounding anatomical areas resulting in abnormal biologicalconditions. As with gonorrhea, staphylococcus infections are especiallyproblematic because certain strains of the bacteria have becomeantibiotic resistant. Infections in the vagina may spread to the uterus,resulting in PID which is often a very painful and serious conditionwith potentially harmful and permanent complications.

In addition to being susceptible to abnormal body conditions caused bybacteria, the vagina and surrounding anatomical areas are susceptible tovarious abnormal body conditions caused by viruses and fungi. Viraldiseases that arise in or affect the vagina and surrounding anatomicalareas include herpes (Types I and II), human papilloma virus (HPV) andHIV, all of which are sexually transmittable. Herpes, HPV and HIV canalso be found in the areas of the mouth, skin and rectum (anus). Fungaldiseases that arise in or affect the vagina include yeast infections,particularly candida, and thrush. Fungi are also responsible forabnormal biological conditions in other areas of the body such as themouth (thrush), feet, skin and nails. There is no cure for herpes andHIV. Anti-viral drugs are available to alleviate herpes symptoms andsuppress the herpes virus so that active infections recur lessfrequently and are of shorter duration, but these drugs are associatedwith significant side effects. Infection with HPV is usually treatedwith topical medications, oral medications and/or surgical removal ofwarts. Complications of HPV infection include increased risk forcervical, rectal and vulvar cancers. Available treatments for HIV aredesigned to suppress the virus and boost the immune system in hope ofavoiding opportunistic infections and delaying or preventing the onsetof full-blown acquired immune deficiency syndrome (AIDS). In recentyears, it was hoped that a vaginal microbicide gel called PRO 2000 wouldbe effective at reducing HIV infection when used shortly before sexualintercourse, but unfortunately the compound was found to be ineffectivein a large scale clinical trial. Topical and oral medications areavailable to treat yeast and other fungal infections, but are limited ineffectiveness such that fungal infections are often not eradicated andthus reoccur. The vast majority of abnormal body conditions caused bybacteria, viruses and fungi that affect the genital and/or rectal areasin women also affect the genital and/or rectal areas in men.

In addition to conditions caused by harmful pathogens or microbes,hemorrhoids are another abnormal body condition that affects the rectum(anus) in men and women and may cause rectal pain, swelling, discomfortand/or itching. Conventional treatments for hemorrhoids include topicalmedications and surgery.

In addition to harmful microbes and pathogens, sperm may appear in thevagina after intercourse. Numerous spermicidal contraceptive compoundsare available for introduction in the vagina. Typically, these must beintroduced in the vagina very shortly before intercourse and aretherefore oftentimes inconvenient. When intercourse takes place withoutcontraception and there is concern for an unwanted pregnancy, drugsknown as the “morning after pill” or “emergency contraceptives” aresometimes prescribed to prevent pregnancy, but these drugs are not 100%effective and may have undesirable side effects.

Abnormal body conditions of bacterial, viral and fungal origins commonlyarise in dermatological areas of the body, i.e. skin and nails. The skinand soft tissue are common sites for infections caused by variousbacteria including staphylococcus, enterobacter, pseudomonas, andstreptococcus. Oftentimes, infections develop on the skin at the site ofa cut, scratch, abrasion, burn, splinter, boil, pimple, blister, insectbite or other wound or trauma that damages or breaks the skin orprovides a point of entry for bacteria and/or other harmful organisms.Viruses such as herpes, shingles and HPV are also the cause of abnormalbody conditions on the skin. In particular, herpes causes cold sores(fever blisters), shingles causes painful eruptions, and HPV causeswarts on the skin. Other organisms also cause warts on the skin. Theskin is susceptible to various fungal conditions, such as “athlete'sfoot” which commonly occurs on the feet and rashes such as ringworm.Infections of the nails, particularly fungal infections of the toenails,are also a common and tenacious problem. The skin is further susceptibleto various body conditions resulting from aging, environmental factorsand various external and internal causes, such conditions includingsun/wind damage, dry skin, age spots, pigmentation, scarring, blisters,bolls, cysts, pimples, cuts, scratches, burns, abrasions, splinters,insect bites and stings, animal bites and scratches, ulcers, loss ofelasticity or collagen that manifests as wrinkles and sagging skin,acne, and many types of rashes, such as measles, chicken pox, eczema,psoriasis, impetigo and rosacea, due to various underlying external andinternal causes. Various topical and oral prescription andnon-prescription medications and products are available to treat theforegoing skin conditions. The skin is also a carrier for bacteria,viruses and fungi, seeing as how the skin regularly comes in contactwith a plethora of pathogens and microbes. Consequently, many productssuch as sanitizing hand and body lotions and wipes are availablecommercially for the purpose of reducing germs on the skin.

The oral-respiratory-otic areas of the body, i.e. mouth, throat, nose,sinuses and ears are also common sites for abnormal body conditions dueto the aforementioned pathogens and microbes. In addition, variousallergies cause undesirable body conditions that impact theoral-respiratory-otic areas of the body, particularly the throat, noseand sinuses. Asthma is a chronic inflammatory disease of the airwaysresponsible for undesirable conditions. Bacteria, viruses, fungi,allergies and/or asthma are responsible for many unwanted symptoms thatappear in the oral-respiratory-otic areas of the body including sorethroat, tonsillitis, colds, bronchitis, sinusitis, rhinosinusitis,wheezing, ear infections, earache, pressure in the ears, cold sores,mouth ulcers, canker sores, cough, hoarseness or laryngitis, congestion,runny nose, sneezing, sore gums, periodontal disease, tooth decay andhalitosis (bad breath). A vast array of prescription andnon-prescription drugs and products are commercially available to treatoral-respiratory-otic conditions.

The prescription drugs and even many of the non-prescription drugs orproducts used to treat the numerous body conditions described above havemany drawbacks including undesirable or potentially harmful sideeffects, high risk of harm in the event of overdose or improper use,high cost, limited effectiveness, the need for close medical monitoring,and inconvenience. Moreover, there is presently no single compound orproduct to treat a wide range of body conditions affecting thegenital-rectal areas that include the vagina, rectum (anus), andsurrounding anatomical areas, the oral-respiratory-otic areas thatinclude the mouth, throat, airway, nose, sinuses and ears, and thedermatological areas that include the skin and nails, much less anon-pharmaceutical topical treatment that is safe, cost-effective, easyand convenient to use, and capable of being embodied in different formsdepending on the intended anatomical area or areas of use.

It has previously been established that copper possesses properties bywhich it is capable of killing, neutralizing and preventing the growthof human pathogens. It is known that many bacteria identified as humanpathogens cannot survive on surfaces of copper metal. U.S. Pat. No.8,135,466 B2 to Fuller et al discloses a joint prosthesis having animplant body with an external surface containing an antimicrobial metalwhere the antimicrobial metal may be copper. U.S. Patent ApplicationPublications No. US 2012/0071807 A1 and No. US 2012/0089068 A1 toMcClure, Jr. disclose wound dressings containing a metal-basedantimicrobial agent where the metal-based antimicrobial agent may be amixture of silver ions and copper ions. Devices having an externalsurface of copper metal for insertion in the vagina to treat abnormalbiological conditions have been proposed by Applicants in U.S. patentapplication Ser. No. 12/157,823 filed Jun. 13, 2008 (abandoned), Ser.No. 13/317,230 filed Oct. 12, 2011, and Ser. No. 13/464,005 filed May 4,2012, the entire disclosures of which are incorporated herein byreference.

Topical substances containing particles of copper or its alloys havebeen proposed for health support uses. A product called “MesoCopper®”sold by Purist Colloids, Inc. is a colloidal copper solution containingnanoparticles of copper for use on the skin to minimize the appearanceof fine lines and wrinkles. Another version of the product is sold as aningestible mineral supplement. Copper peptides for use on the skin arealso commercially available and these require peptides, i.e. smallfragments of protein that have an affinity for copper to which they bindvery tightly. U.S. Pat. No. 7,776,915 B2 to Morariu discloses a topicalcomposition containing, at a minimum, a lipoic acid, a carnitine and acarnosine, where the carnosine may be chelated to zinc or copper ions.The intended use for the topical composition is to improve theappearance of aged skin. U.S. Patent Application Publication No.US2008/0195033 A1 to Eagleson et al discloses use of a metal substanceto treat diseases in the body. The metal substance is primarily acolloidal suspension and delivery of the substance to the body mayrequire the use of electricity. Prior to the present disclosure, it hasnot been recognized to provide a simple solution containing copper ionsfor use as a topical treatment to be applied directly to anatomicaltissue to treat body conditions and/or for use in conjunction withvarious carriers including creams, gels, lotions, foams, pastes, othersolutions, suppositories, tampons, body wipes, wound dressings, skinpatches and suture material to form topical treatments in which thecarriers facilitate delivery of the copper ions to contact anatomicaltissue depending on the anatomical area or areas of use on the body.

SUMMARY OF THE DISCLOSURE

The present disclosure pertains generally to treatments containingcopper ions and to methods of treating conditions in various anatomicalareas of the body using such formulations. Some embodiments of thepresent disclosure pertain to topical treatments containing copper ionsand to methods of making such topical treatments wherein copper ionsfrom copper metal are leached into a solution. In certain embodiments,the present disclosure pertains to methods of using such topicalformulations to treat osteoarthritis.

In some embodiments, the present disclosure provides methods of treatingosteoarthritis of a joint comprising, administering a pharmaceuticallyacceptable topical formulation comprising copper ions 1-3 times daily toa human in need of such treatment. In certain embodiments, the joint isa knee, a hip, an elbow, a hand joint, a spine or a toe. In certainembodiments, the joint is a knee joint.

In some aspects of the present disclosure, a patient with a jointdisease achieves a Visual Analog Scale (VAS) score that is at least 15units lower than the baseline VAS score following treatment with acopper ion containing formulation of the present disclosure. In someaspects of the present disclosure, a VAS score that is at least 25 unitslower than the baseline VAS score is achieved.

In some aspects of the present disclosure, a patient with a jointdisease achieves a Western Ontario and McMaster Universities ArthritisIndex (WOMAC) score that is at least 4 units lower than the baselineWOMAC score, following treatment with a copper ion containingformulation of the present disclosure.

Some embodiments provide a pharmaceutically acceptable copper ionformulation that is a cream, lotion, gel or a foam, and methods oftreatment wherein said cream, lotion, gel or foam is applied topically.In certain embodiments, the pharmaceutically acceptable formulation is acream, such as 3VM1001 cream. The present disclosure includesformulations wherein at least 10 μg/mL copper ion is present in theliquid phase. In some embodiments, the pharmaceutically acceptableformulation comprises about 11.5 μg/mL copper ion in the liquid phase.

In some embodiments, a copper ion formulation according to the presentdisclosure is applied topically every other day. In other embodiments, acopper ion formulation according to the present disclosure is appliedtopically 1, 2, 3, 4 or 5 times per day. In certain embodiments, acopper ion formulation according to the present disclosure is appliedevery 2-24 hrs.

In certain embodiments, 0.5-10 g of a copper ion formulation is appliedat each administration. In some of these embodiments, 0.5 g, 1 g, 1.5 g,2 g, 2.5, 3, 3.5, 4, 4.5 or 5 g is applied at each administration. Incertain embodiments, 0.5 g, 1 g, 1.5 g, 2 g, 2.5, 3, 3.5, 4, 4.5 or 5 gof a copper ion containing cream is applied at each administration. Incertain embodiments, 2 g of a copper ion containing cream is applied 1-3times/day. In some embodiments, 2 g of a copper ion containing cream isapplied 3 times/day.

The present disclosure further provides methods of making a copper ioncream from wherein the copper present in the liquid phase issubstantially enhanced. In some of these embodiments, the copperconcentration in the liquid phase is substantially enhanced compared tothe copper concentration in the liquid phase of a bulk suspension usedto prepare the cream. In certain embodiments, the copper concentrationin the liquid phase of the cream is at least 5-10 μg/mL or at least10-15 μg/mL. In certain embodiments, the copper concentration in theliquid phase of the cream is about 11.5 μg/mL.

According to an aspect of the present disclosure, a topical copper iontreatment is prepared by a process whereby copper ions from copper metalleach into a biocompatible solution. The copper metal in solid form isplaced into the solution in a sealed vessel, and the sealed vessel isplaced in an oven to heat or maintain the solution at a temperatureequal or substantially equal to 37° Celsius for a predetermined periodof time during which copper ions leach from the copper metal into thesolution, where they may form insoluble salts by combining withnegatively charged counter-ions, such as phosphate. After the period oftime has expired, the solution is separated from the copper metal andconstitutes a copper ion-containing solution that can be used as acopper ion treatment for topical application to anatomical tissue invarious areas of the body to treat various body conditions. Preferably,the biocompatible solution is a saline solution and the copper metal ispure copper. A copper ion-containing solution or suspension obtained inaccordance with a preferred process results in an amount of copper ionsequal or substantially equal to 46 mg present in 7.44 ounces of thecopper ion-containing solution or suspension.

According to another embodiment of the present disclosure, a bulksuspension comprising precipitated copper salts is prepared byincubating a buffered saline solution with copper metal. The resultingbulk suspension is subsequently combined with a cream base to yield acream wherein a substantial proportion of the copper from the bulksuspension is found in the soluble phase. In certain embodiments, atleast 5 μg/mL, 7 μg/mL, 9 μg/mL or 11 μg/mL of copper is found in thesoluble phase. In some embodiments, the liquid phase of the creamcontains about 11.5 μg/mL.

According to yet another embodiment of the present disclosure, methodsof preventing biofilm formation by administering a formulationcomprising copper to a human in need of such treatment are provided. Insome of these methods, the formulation is a suspension prepared byincubating phosphate buffered saline with copper metal. In certainembodiments, the suspension prevents formation of biofilm by at leastone of the following bacterial species: Streptococcus mutans,Gardnerella vaginalis, Neisseria gonorrhoeae, Mobiluncus curtisii,Atopobium vaginae and Chlamydia trachomatis.

In certain embodiments, the copper formulations prevent formation ofdental plaque. The suspension may be administered at least once daily asone tablespoon of a copper ion suspension. In some embodiments, thecopper ion suspension is 3VM1000. In some aspects of the presentdisclosure, the copper formulations prevent oral biofilm formation byStreptococcus mutans.

The present disclosure also provides compositions and methods forpreventing and treating viral infections, particularly infections by thehuman immunodeficiency virus, type 1 (HIV-1). In some embodies, a cream,gel, or a suppository of the present disclosure is administered toprevent HIV-1 infection.

The copper ion-containing solution can be combined with various carriersto facilitate application or delivery of the copper ion-containingsolution to anatomical tissue in accordance with the anatomical area orareas of use. Suitable carriers include creams, lotions, gels, foams,pastes, other solutions, tampons, suppositories, body wipes, wounddressings, skin patches and suture material to obtain other forms ofcopper ion treatments. Various devices such as containers, bottles andtubes can be used to dispense the copper ion treatments in a manner bestsuited for the form of copper ion treatment and/or the intendedanatomical area or areas of use. The copper ion treatments areparticularly advantageous for use on anatomical tissue of thegenital-rectal areas, the oral-respiratory-otic areas and thedermatological areas of the body.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a front view of a bottle containing a copper ion treatment andhaving a spray pump nozzle for dispensing the copper ion treatment.

FIG. 2 is a side view of a bottle containing a copper ion treatment andhaving a spray pump nozzle with an elongate extension for dispensing thecopper ion treatment.

FIG. 3 is a side view of a bottle containing a copper ion treatmentwherein the bottle is squeezable to dispense the copper ion treatmentfrom a dropper on the bottle.

FIG. 4 is a side view of a bottle containing a copper ion treatment andhaving a brush for applying the copper ion treatment to anatomicaltissue.

FIG. 5 is a side view of a tube containing a copper ion treatmentwherein the tube is squeezable to dispense the copper ion treatment.

FIG. 6 is a side view of an alternative bottle that is squeezable todispense a copper ion treatment and showing the bottle in a dosedcondition.

FIG. 7 is a side view of the bottle of FIG. 6 showing the bottle in anopen condition.

FIG. 8 is a side view of a bottle containing a copper ion treatment andhaving a pump nozzle for dispensing the copper ion treatment in the formof foam.

FIG. 9 is a side view of an applicator for delivering a copper iontreatment to the vagina.

FIG. 10 is a side view of the applicator of FIG. 9 showing use of theapplicator in conjunction with the tube of FIG. 5.

FIG. 11 is a side view of an alternative applicator for applying acopper ion treatment onto anatomical tissue.

FIG. 12 is a side view of a tampon having a tampon body used as acarrier to deliver a copper ion treatment to the vagina.

FIG. 13 is a broken front view of a plurality of suppositoriescontaining a copper ion treatment, the suppositories being insertable inthe vagina or rectum to deliver the copper ion treatment to the vaginaor rectum.

FIG. 14 is a side view showing a suppository of FIG. 13 being removedfrom its package.

FIG. 15 is a side view of an applicator for delivering the suppositoriesof FIG. 13 to the vagina or rectum.

FIG. 16 is a front view of a package containing a body wipe carrying acopper ion treatment and showing the package partially open to removethe body wipe therefrom.

FIG. 17 is a perspective view of a wound dressing supplied with a copperion treatment.

FIG. 18 is a plan view of a skin patch carrying a copper ion treatment.

FIG. 19 is a perspective view of sutures created in anatomical tissueusing suture material carrying a copper ion treatment.

FIG. 20 shows the mean change from baseline in daily VAS forosteoarthritis patients treated with 3VM1001.

FIG. 21 shows the mean change from baseline in daily WOMAC score forosteoarthritis patients treated with 3VM1001.

FIG. 22 shows copper strips separated by using stainless steel rods in aphosphate buffered saline solution.

FIG. 23 shows the bulk suspension obtained after incubating phosphatebuffer saline with copper strips.

FIG. 24 shows the transfer of the bulk suspension to a measuring cup.

FIG. 25 shows the bulk suspension following transfer to a clean glassdish.

DETAILED DESCRIPTION OF EMBODIMENTS

Provided herein are topical formulations comprising copper ions for thetreatment of a variety of conditions, including inflammatory conditions.In particular, methods of treating osteoarthritis using topical copperion formulations such as a copper ion cream are provided. Inasmuch asthe present disclosure is subject to many variations, modifications andchanges in detail, it is intended that all subject matter discussedabove or shown in the accompanying drawings be interpreted asillustrative only and not be taken in a limiting sense.

In some embodiments, a solution containing copper ions, i.e. copperion-containing solution, for use as a topical treatment containingcopper ions, i.e. topical copper ion treatment, to treat body conditionsis produced according to a process or method by which copper ions fromcopper metal are leached into an appropriate biocompatible solution. Asused herein, “copper metal” means pure copper (99.5% or greater copperafter processing) and copper alloys such as brasses, bronzes,copper-nickels and copper-nickel-zincs. Preferably, pure copper is usedas the copper metal. Example 1 describes the steps involved in producingan amount of copper ion-containing solution equal or substantially equalto 7.44 ounces.

In other embodiments, a suspension containing a copper salt precipitateis combined with a cream base to create a copper ion cream, wherein asubstantial proportion of the copper ions are found in the liquid phaseof the cream. In certain embodiments, at least 5 μg/mL, 7 μg/mL, 9 μg/mLor 11 μg/mL of copper is found in the soluble phase. In someembodiments, the liquid phase of the cream contains about 11.5 μg/mL ofcopper. Example 34 describes the steps involved in preparing a creamwith about 11.5 μg/mL of copper in the soluble phase.

Inasmuch as the present disclosure is subject to many variations,modifications and changes in detail, it is intended that all subjectmatter discussed above or shown in the accompanying drawings beinterpreted as illustrative only and not be taken in a limiting sense.

EXAMPLES Example 1

7.44 ounces of biocompatible saline solution buffered with acetic acidand sodium acetate to a pH of 5 (±0.4) is placed in a container orvessel with a tight, removable lid to minimize evaporation. Thecontainer is placed in an incubator or oven at a temperature of 37°Celsius (±1° C.). When the saline solution has reached 37° Celsius, 102grams of pure copper metal in solid form is placed in the heatedsolution within the container, and the container with the tight lidthereon is placed in the incubator at 37° Celsius for 24 hours. Duringthe 24 hour period, copper ions from the copper metal leach into thesolution. At the end of the 24 hour period, the container is removedfrom the incubator and the copper metal is removed or separated from thesolution. The amount of solution remaining after removal or separationof the copper metal therefrom constitutes the copper ion-containingsolution and should be essentially 7.44 ounces with minimal evaporation.The copper ion-containing solution produced according to this processcontains copper ions in an amount equal or substantially equal to 46milligrams when analyzed for copper content by inductively coupledplasma/optical emission spectroscopy (ICP/OES). The copperion-containing solution is stored at room temperature and is ready foruse in this form as a topical copper ion treatment to be applied toanatomical tissue to treat body conditions. In addition, the copperion-containing solution is ready for use in conjunction with variouscarriers including creams, gels, lotions, foams, pastes, othersolutions, suppositories, tampons, body wipes, wound dressings, skinpatches and suture materials to form topical copper ion treatments inwhich the carriers facilitate delivery of the copper ion treatments tocontact anatomical tissue to treat body conditions.

The solid pure copper metal in Example 1 may be in the form of one ormore sheets of pure copper metal, typically in the range of 0.03 to 0.06inch thick, of appropriate length and width to provide the 102 grams ofpure copper metal. In practice, the process described in Example 1 hasbeen carried out using as the copper metal four vaginal therapeuticdevices made of pure copper in accordance with Applicants' prior patentapplication Ser. No. 13/464,005 previously incorporated herein byreference in its entirety. In this case, each vaginal therapeutic deviceused was 3.25 Inches long by 0.750 inch wide with a wall thickness of0.031 inch providing 25.5 grams of pure copper. The biocompatible salinesolution used in the process described in Example 1 is commerciallyavailable from B. Braun Medical. As an alternative to the biocompatiblesaline, vaginal simulating fluid (VSF) buffered with acetic acid to a pHof 5 (±0.4) can be used as the biocompatible solution, but will produceless leaching of copper ions from copper metal over the 24 hour period.The VSF can be prepared in accordance with published literature, e.g.Owen, D. H., Katz, D. F., “A Vaginal Fluid Simulant”, Contraception,pages 91-95 (1999). The process described in Example 1 can be modifiedto eliminate the step of heating the solution prior to placement of thecopper metal therein. In the latter case, the copper metal and unheatedsolution are placed in the container, the container with the tight lidthereon is placed in the Incubator at 37° Celsius and, once the solutionhas reached 37° Celsius, the container with the heated solution andcopper metal therein is allowed to remain in the oven for 24 hours. Thecopper metal can be removed or separated from the solution in variousways, such as by lifting the metal out of the solution or pouring thesolution alone into another container. Of course, the quantities ofbiocompatible saline and solid copper mental used in Example 1 can beproportionately increased to produce a greater amount of copperion-containing solution with each process.

The copper ion-containing solution is believed to have the greatesteffectiveness for treating a wide range of body conditions when thesolution contains the amount of copper ions leached into the saline fromthe 46 mg copper metal over a 24 hour period as described in Example 1.However, it should be appreciated that the process described in Example1 can be modified to obtain lower copper ion concentrations by adjustingthe length of time that the container containing the heated saline andcopper metal is allowed to remain in the incubator or oven as explainedbelow in Examples 2, 3 and 4.

Example 2

This Example follows the steps of Example 1 except that the containercontaining the saline and copper metal to remain in the oven at 37° C.for one hour to obtain a copper ion-containing solution that contains anamount of copper ions equal or substantially equal to 8.8 mg.

Example 3

This Example follows the steps of Example 1 except that the containercontaining the saline and copper metal to remain in the oven at 37° C.for eight hours to obtain a copper ion-containing solution that containsan amount of copper ions equal or substantially equal to 22 mg.

Example 4

This Example follows the steps of Example 1 except that the containercontaining the saline and copper metal to remain in the oven at 37° C.for 72 hours to obtain a copper ion-containing solution that contains anamount of copper ions equal or substantially equal to 35 mg.

The copper ion-containing solution in its original form. i.e. at the endof the processes of Examples 1-4, can be applied directly to anatomicaltissue in various anatomical areas of the body as a copper ion treatmentto treat various body conditions. Many types of containers or bottlescan be used to hold a quantity of the copper ion-containing solution andto dispense or apply the copper ion-containing solution to anatomicaltissue in accordance with the intended anatomical area or areas of use.The copper ion-containing solution may also be used in conjunction withvarious carriers including creams, lotions, gels, foams, pastes, othersolutions, tampons, suppositories, body wipes, wound dressings such asband aids and pads, skin patches and suture material to form copper iontreatments that facilitate delivery or application of the copperion-containing solution, and therefore the copper ions, to anatomicaltissue. Creams, lotions, gels, foams and pastes may be used when it isadvantageous to alter the consistency of the copper ion-containingsolution from its original form to obtain a thicker copper ion treatmentto facilitate its delivery or application to anatomical tissue. As aresult of the copper ions contacting anatomical tissue when the copperion treatments are applied thereto, local and systemic therapeuticeffects are realized including antibacterial, antimicrobial, antiseptic,antifungal, antiviral, anti-pathogenic, anti-inflammatory, spermicidal,neutralization of free radicals, promotion of healing and tissue repair,prevention of biofilm, and immune-boosting effects. In particular, theseeffects are realized when the copper ion treatments are used onanatomical tissue in the genital-rectal areas, the oral-respiratory-oticareas and the dermatological areas of the body since the anatomicaltissue in these areas is favorable for local and systemic delivery ofdrugs and medicaments.

In accordance with an aspect of the present disclosure, the copperion-containing solution is combined with an appropriate topical creambase to form a copper ion-containing cream, i.e. copper ion cream inwhich the amount of copper ion-containing solution is preferably in therange of 5% to 30% by weight of the total weight of the copper ioncream. Examples 5, 6, 7 and 8 pertain to copper ion creams made inaccordance with this aspect of the present disclosure using the copperion-containing solution of Example 1.

Example 5

An appropriate amount of copper ion-containing solution is combined witha biocompatible topical cream base to form a copper ion cream in whichthe copper ion-containing solution constitutes 5 percent of the totalweight of the copper ion cream.

Example 6

An appropriate amount of copper ion-containing solution is combined witha biocompatible topical cream base to form a copper ion cream in whichthe copper ion-containing solution constitutes 10 percent of the totalweight of the copper ion cream.

Example 7

An appropriate amount of copper ion-containing solution is combined witha biocompatible topical cream base to form a copper ion cream in whichthe copper ion-containing solution constitutes 20 percent of the totalweight of the copper ion cream.

Example 8

An appropriate amount of copper ion-containing solution is combined witha biocompatible topical cream base to form a copper ion cream in whichthe copper ion-containing solution constitutes 30 percent of the totalweight of the copper ion cream.

Various topical cream bases can be used as the carrier for the copperion-containing solution in order to form the copper ion creams ofExamples 5, 6, 7 and 8. One suitable topical cream base that can be usedis VersaBase® cream made by Professional Compounding Centers of America(PCCA) of Houston, Tex. Another suitable topical cream base that can beused in the copper ion creams is Vanicream® made by PharmaceuticalSpecialties, Inc. of Rochester, Minn. The copper ion creams areeffective against the body conditions being treated when the only activeingredient in the copper ion creams directed at the underlying conditionis the copper ion-containing solution. However, the copper ion creamscould contain other ingredients added to the topical cream base that arenot active ingredients with respect to the underlying condition beingtreated such as preservatives, penetrating additives, bioadhesives andstability aids. Preferably, a total weight of at least 70 grams, morepreferably 80 grams, of the copper ion creams in the various strengths.i.e. 5 percent, 10 percent, 20 percent and 30 percent of copperion-containing solution relative to the total weight of the copper ioncream, will be provided for use in containers, bottles, or tubes fromwhich the copper ion creams can be dispensed. It should be appreciatedthat copper ion creams can be made using the alternative copperion-containing solutions described above.

According to a further aspect of the present disclosure, a topicalcopper ion treatment in the form of a copper ion-containing gel, i.e.copper ion gel, is composed of the copper ion-containing solution and asuitable topical gel base as illustrated below by Examples 9, 10, 11 and12, which utilize the copper ion-containing solution of Example 1. Theamount of the copper ion-containing solution in the copper ion gel ispreferably in the range of 5% to 30% by weight of the total weight ofthe copper ion gel.

Example 9

An appropriate amount of copper ion-containing solution is combined witha biocompatible topical gel base to form a copper ion gel in which thecopper ion-containing solution constitutes 5 percent of the total weightof the copper ion gel.

Example 10

An appropriate amount of copper ion-containing solution is combined witha biocompatible topical gel base to form a copper ion gel in which thecopper ion-containing solution constitutes 10 percent of the totalweight of the copper ion gel.

Example 11

An appropriate amount of copper ion-containing solution is combined witha biocompatible topical gel base to form a copper ion gel in which thecopper ion-containing solution constitutes 20 percent of the totalweight of the copper ion gel.

Example 12

An appropriate amount of copper ion-containing solution is combined witha biocompatible topical gel base to form a copper ion gel in which thecopper ion-containing solution constitutes 30 percent of the totalweight of the copper ion gel.

Various topical gel bases can be used as a carrier for the copperion-containing solution in order to form the copper ion gels. An exampleof a suitable topical gel base that can be used in Examples 9-12 isVersaBase® gel made by PCCA. As explained above for the copper ioncreams, the copper ion gels will be effective when the only activeingredient in the copper ion gels is the copper ion-containing solution,but other ingredients that are inactive with respect to the underlyingcondition being treated can be added to the topical cream gels.Preferably, a total weight of at least 70 grams, more preferably 80grams, of the copper ion gels in the various strengths, i.e. 5 percent10 percent, 20 percent and 30 percent of copper ion-containing solutionrelative to the total weight of the copper ion gel, is provided for usein containers, bottles or tubes from which the copper ion gels can bedispensed. Also, copper ion gels can be made using the alternativecopper ion-containing solutions. Copper ion gels can be made having athin, fluidic consistency, and such gels may be used as copper ionserums.

A topical copper ion treatment in the form of a copper ion-containinglotion, i.e. copper ion lotion, according to an additional aspect of thepresent disclosure is composed of the copper ion-containing solution anda suitable topical lotion base as represented by Examples 13, 14, 15 and16. Examples 13-16 employ the copper ion-containing solution of Example1, but copper ion lotions could be made using the alternative copperion-containing solutions. The amount of the copper ion-containingsolution in the copper ion lotion is preferably in the range of 5% to30% by weight of the total weight of the copper ion lotion. Copper iongels can be made having a thin, fluidic consistency, and such gels maybe used as copper ion serums.

Example 13

An appropriate amount of copper ion-containing solution is combined witha biocompatible topical lotion base to form a copper ion lotion in whichthe copper ion-containing solution constitutes 5 percent of the totalweight of the copper ion lotion.

Example 14

An appropriate amount of copper ion-containing solution is combined witha biocompatible topical lotion base to form a copper ion lotion in whichthe copper ion-containing solution constitutes 10 percent of the totalweight of the copper ion lotion.

Example 15

An appropriate amount of copper ion-containing solution is combined witha biocompatible topical lotion base to form a copper ion lotion in whichthe copper ion-containing solution constitutes 20 percent of the totalweight of the copper ion lotion.

Example 16

An appropriate amount of copper ion-containing solution is combined witha biocompatible topical lotion base to form a copper ion lotion in whichthe copper ion-containing solution constitutes 30 percent of the totalweight of the copper ion lotion.

Various topical lotion bases can be used as a carrier for the copperion-containing solution in the copper ion lotions of Examples 13-16. Onesuitable topical lotion base that can be used is VersaBase® lotion madeby PCCA. As explained above for the copper ion creams and gels, thecopper ion lotions will be effective against the body conditions beingtreated when the only active ingredient in the copper ion lotions is thecopper ion-containing solution, but other inactive ingredients could beadded to the topical lotion base. Preferably, a total weight of at least70 grams, more preferably 80 grams, of the copper ion lotions in thevarious strengths, i.e. 5 percent, 10 percent, 20 percent and 30 percentof copper ion-containing solution relative to the total weight of thecopper ion lotion, will be provided for use in containers, bottles ortubes from which the copper ion lotions can be dispensed.

According to another aspect of the present disclosure, a topical copperion treatment in the form of a copper ion-containing foam, i.e. copperion foam, is composed of the copper ion-containing solution and asuitable foam base. Examples 17, 18, 19 and 20 set forth below pertainto copper ion foams or foamable solutions made in accordance with thisaspect of the present disclosure using the copper ion-containingsolution of Example 1, however copper ion foams or foamable solutionscan be made using the alternative copper ion-containing solutions. Theamount of the copper ion-containing solution in the copper ion foam orfoamable solution is preferably in the range of 5% to 30% by weight ofthe total weight of the copper ion foam or foamable solution.

Example 17

An appropriate amount of copper ion-containing solution is combined witha biocompatible topical foam base to form a copper ion foam or foamablesolution in which the copper ion-containing solution constitutes 5percent of the total weight of the copper ion foam or foamable solution.

Example 18

An appropriate amount of copper ion-containing solution is combined witha biocompatible topical foam base to form a copper ion foam or foamablesolution in which the copper ion-containing solution constitutes 10percent of the total weight of the copper ion foam or foamable solution.

Example 19

An appropriate amount of copper ion-containing solution is combined witha biocompatible topical foam base to form a copper ion foam or foamablesolution in which the copper ion-containing solution constitutes 20percent of the total weight of the copper ion foam or foamable solution.

Example 20

An appropriate amount of copper ion-containing solution is combined witha biocompatible topical foam base to form a copper ion foam or foamablesolution in which the copper ion-containing solution constitutes 30percent of the total weight of the copper ion foam or foamable solution.

Various topical foam bases can be used as a carrier for the copperion-containing solution in order to form the copper ion foams orfoamable solutions. Depending on the foam base used in Examples 17-20,the combination of foam base and copper ion-containing solution may bein the form of a foam. Alternatively, some foam bases that may be usedwill result in a foamable solution when combined with the copperion-containing solution, and the foamable solutions will typicallyrequire an appropriate dispenser to create the actual foam. An exampleof a suitable topical foam base that can be used is VersaBase® foam madeby PCCA. When using VersaBase® as the foam base in Examples 17-20, afoamable solution is obtained and requires a foam dispenser to createthe foam. As explained above for the copper ion creams, gels andlotions, the copper ion foams win be effective against the bodyconditions being treated with the only active ingredient therein beingthe copper ion-containing solution. However, other ingredients that areinactive with respect to the condition being treated can be added to thetopical foam base. It is preferred that a total weight of at least 70grams, more preferably 80 grams, of the copper ion foams or foamablesolutions in the various strengths, i.e. 5 percent, 10 percent, 20percent and 30 percent of copper ion-containing solution relative to thetotal weight of the copper ion foam or foamable solution, be provided indispensers from which the copper ion foams can be dispensed.

According to a further aspect of the present disclosure, a topicalcopper ion treatment in the form of a copper ion-containing paste, i.e.copper ion paste, is composed of the copper ion-containing solution anda suitable paste base. Example 21 set forth below pertains to a copperion toothpaste made in accordance with this aspect of the presentdisclosure using the copper ion-containing solution of Example 1, butcopper ion pastes can also be made using the alternative copperion-containing solutions. The amount of the copper ion-containingsolution in the copper ion pastes is preferably in the range of 5% to30% by weight of the total weight of the copper ion paste.

Example 21

An appropriate amount of copper ion-containing solution is combined witha toothpaste base material to form a copper ion toothpaste in which thecopper ion-containing solution constitutes in the range of 5 percent to30 percent of the total weight of the copper ion toothpaste.

The toothpaste base material used in Example 21 can be a commerciallyavailable toothpaste including any of the toothpastes marketed and soldunder the major brand names. A toothpaste made in accordance withExample 21 is advantageous for treating bad breath, sore gums, gumdiseas, plaque, biofilm and tooth decay when used on a daily basis inplace of a person's regular toothpaste.

According to a further aspect of the present disclosure, the copperion-containing solution can be combined with various base solutions toform alternative copper ion solutions. Example 22 set forth belowpertains to a copper ion mouthwash made in accordance with this aspectof the present disclosure using the copper ion-containing solution ofExample 1, but copper ion solutions can also be made using thealternative copper ion-containing solutions of Examples 2-4. The amountof copper ion-containing solution in the alternative copper ion solutionis preferably in the range of 5% to 30% by weight of the total weight ofthe copper ion solution.

Example 22

An appropriate amount of copper ion-containing solution is combined witha mouthwash base solution to form a copper ion mouthwash in which thecopper ion-containing solution constitutes in the range of 5 percent to30 percent of the total weight of the copper ion mouthwash.

The mouthwash base solution used in Example 22 can be a commerciallyavailable mouthwash including any of the mouthwashes marketed and soldunder the major brand names. A mouthwash made in accordance with Example22 is advantageous for treating bad breath, sore gums, periodontaldisease and tooth decay when used on a daily basis.

The examples described above pertaining to carriers in the nature oflotions, gels, foams and other solutions are particularly well suitedfor creating copper ion treatments in the nature of copper ion soaps byusing as carriers lotion, gel, foam or other solution bases containing asoap component. The copper ion soaps could be designed for use as bodysoaps or as dish soaps.

FIG. 1 depicts a device 10 useful for dispensing the copper iontreatments, particularly the copper ion-containing solutions in theiroriginal form, e.g. the form resulting from Examples 1-4, and the copperion lotions. The device 10 comprises a container or bottle 12 forholding the copper ion-containing solution and having a spray pumpnozzle 14 with an outlet orifice 16. The spray pump nozzle 14 isresiliently biased, typically by a spring, in an upward direction awayfrom the container 12 but is depressible in a downward direction towardthe container 12 to effect the spray pump action. Each time the spraypump nozzle is manually depressed the full amount, typically using afinger of the hand holding the container, a predictable amount of copperion-containing solution is discharged in the form of a spray or streamfrom the outlet orifice 16. The container 12 may include a removableprotective cover 18 for being disposed over the spray pump nozzle 14between uses. In use, the outlet orifice 16 is placed in line withanatomical tissue to be treated at a close enough distance that thetissue is within the range of the spray or stream dispensed from theoutlet orifice. The spray pump nozzle 14 is then depressed the fullamount using a finger, causing the predictable amount of copperion-containing solution to be delivered or sprayed onto the anatomicaltissue. The spray pump nozzle 14 can, of course, be depressed multipletimes to deliver multiple sprays or streams of the copper ion-containingsolution to the tissue. The device 10 could also be adapted to dispensethe copper ion lotions in a similar manner, although in such case thecopper ion lotions would typically be dispensed in the form of a ribbon,mass or stream of material. In the latter case, the copper ion lotionscould be dispensed directly on the tissue to be treated, or on the palmor fingers of a hand which is then used to apply the lotions on thetissue to be treated. The copper ion lotions may be best suited for useon the skin, on the external genital and rectal areas, and in thevagina.

Another device 20 useful for dispensing the copper ion treatments,particularly the copper ion-containing solution in its original form, isshown in FIG. 2. The device 20 is similar to the device 10 and comprisesa container or bottle 22 having a spray pump nozzle 24 with an outletorifice 26. The device 20, however, further includes an elongate hollowextension 28 attached to the spray pump nozzle 24. The extension 28 hasa first end coupled with the outlet orifice 26 of the spray pump nozzle24 and has an opposed second end with a wider end surface having adischarge opening 29. Preferably, a plurality of discharge openings 29are provided along the wider end surface as shown in dotted lines inFIG. 2 to obtain a wider spray pattern as indicated by dotted lines.Each time the spray pump nozzle 24 is manually depressed the fullamount, a predictable amount of copper ion treatment is released inspray form from the discharge openings 29 at the end of the extension28. The wider end surface and plurality of discharge openings at thesecond end of the extension provides a wider spray pattern than thedevice 10. The device 20 could be designed without the spray pumpnozzle, with the container 22 being squeezable to force the copper iontreatment to be discharged from the discharge opening(s) 29. Theextension 28 may be selectively detachable/attachable to the spray pumpnozzle 24 for ease of storage of the device 20. The device 20 mayinclude a removable protective cover (not shown) for being placed overthe nozzle 24 between uses. The device 20 is particularly useful as anatomizer for dispensing the copper ion treatments to contact anatomicaltissue deeper within the mouth, throat and airway.

The device 30 depicted in FIG. 3 is also useful for dispensing thecopper ion treatments, particularly the copper ion-containing solutionin its original form. The device 30 comprises a squeezable container orbottle 32 for holding the copper ion treatment and having a tapereddropper or extension 34 with an outlet orifice 36 attached to a cap onthe container 32. In use, the container 32 is positioned so that theoutlet orifice 36, which is located at the tip of the dropper, facesanatomical tissue to be treated. The container 32 is then squeezed withthe fingers and, in response to such finger pressure, individual dropsof a predictable amount of copper ion treatment are released from theoutlet orifice 36. Alternatively, the extension 34 can be designed todischarge the copper ion treatment in the form of a spray as shown indotted lines in FIG. 3, which would be particularly useful as anasal/ear spray. The tapered configuration of the dropper/extension 34facilitates its placement in the nostril (nasal cavity) and ear (earcanal). The container 32 may include a removable protective cover 38 forbeing disposed over the dropper 34 between uses. The device 30 isparticularly useful for dispensing the copper ion treatments to contactanatomical tissue within the nose (nostrils), ears (ear canal), skin andnails.

An additional device 40 for dispensing the copper ion treatments isshown in FIG. 4. The device 40 comprises a container or bottler 42 forholding the copper ion treatment and having a removable cap 44 with abrush 45 attached to an underside of the cap. Typically, the cap 44 willbe screwed onto a neck of the container 42. When the cap 44 is disposedon the container 42, the brush 45 extends into the container and isdisposed within the copper ion treatment 43. Upon removal of the cap 44from the container 42, the cap 44 may be manipulated using the fingersand hand to contact anatomical tissue to be treated with the brush 45 inorder to deposit the copper ion treatment from the brush 45 onto theanatomical tissue. The device 40 would be particularly useful forapplying the copper ion treatments on the skin and nails. The brush 45could be eliminated from the cap 44, in which case the device 40, ifsized appropriately, would be advantageous for holding a copper ionsolution such as a copper ion mouthwash.

The device 50 illustrated in FIG. 5 is particularly useful fordispensing the copper ion treatments formed as creams, lotions, gels andpastes. The device 50 comprises a container 52 in the form of asqueezable tube for holding the copper ion treatment and having aremovable cap 54 disposed on an open end or neck 56 of the tube.Typically the cap 54 will be threaded onto an external thread 55 on theneck 56 of the tube. The cap 54 may optionally have a piercing formation57 that may be used to puncture an optional seal covering the open neck56 prior to the first use. Upon removal of the cap 54, the piercingformation 57 is placed against the seal, and the cap 54 is pushed in thedirection of the tube 52 to puncture the seal. Once the seal ispenetrated, the tube 52 can be squeezed, preferably from the bottom ofthe tube working upward, causing the copper ion treatment to bedispensed from the open neck 56 of the tube. The device 50 isparticularly well suited for dispensing the copper ion treatments ontothe fingers or palm of a hand that is then used to apply the treatmentsto anatomical tissue, particularly the tissue of the skin and theexternal genital and rectal areas. However, the copper ion treatmentscould be squeezed directly on the anatomical tissue to be treated. Inaddition, when the copper ion treatment is in a paste or other suitableform for use as a toothpaste, the device 50 is particularly well suitedfor dispensing the copper ion treatment onto a tooth brush in aconventional manner. As explained further below, the device 50 isparticularly well suited for use with a vaginal applicator.

FIGS. 6 and 7 depict an additional device 60 useful for dispensing thecopper ion treatments. The device 60 is particularly advantageous fordispensing copper ion lotions. The device 60 comprises a container orbottle 62 for holding the copper ion treatment and having a cap 64disposed on an open end or neck of the bottle. The cap 64 could beremovable or non-removable. The top surface of the cap 64 is formed by apivotable member or disc 65 having an outlet orifice 66 along a sideedge thereof. FIG. 6 depicts the cap 64 in its closed condition whereinthe pivotable member 65 is in a horizontal position relative to the cap64 and the outlet orifice 66 is disposed within the cap 64 and is notexposed. When the pivotable member 65 is depressed downwardly toward thecontainer 62 at a location opposite the outlet orifice 66 as shown bythe arrow in FIG. 7, the cap 64 will assume the open condition shown inFIG. 7 wherein the pivotable member 65 is disposed at an angle relativeto the cap 64 and the outlet orifice 66 is in an exposed positionlocated slightly above the cap 64. In use, the pivotable member 65 wouldbe depressed using pressure applied with one or more fingers of thehand. With the cap 64 in the open condition as shown in FIG. 7, thecontainer 62 can be squeezed manually to dispense the copper iontreatment therein from the outlet orifice 66. The cap 64 is returned tothe dosed position by pressing downwardly on the pivotable member 65 ata location adjacent the outlet orifice. The device 60 is advantageousfor dispensing the copper ion treatments onto the palm of the hand orfingers used to apply the treatment to anatomical tissue to be treated,but the device 60 could be used to dispense the copper ion treatmentsdirectly on the anatomical tissue to be treated.

The device 70 shown in FIG. 8 is an example of a device that can be usedto dispense the copper ion treatment in the form of a copper ion foam.The device 70 comprises a container 72 for holding the copper ion foamor foamable solution and having a resiliently biased foam pump dispenser74 with an outlet orifice 76. When the foam pump dispenser 74 isdepressed the full amount in a manner similar to the device 10, apredictable amount of the copper ion foam is discharged through theoutlet orifice 76. If necessary, the device 70 may include a mechanismfor creating foam as the copper ion treatment is discharged therefrom.The device 70 may have a removable protective cover 78 for beingdisposed over the foam pump dispenser 74 between uses. The device 70could also be adapted to dispense copper ion lotions and gels.

FIG. 9 depicts a vaginal applicator 81 useful for delivering the copperion treatments to the vagina. The vaginal applicator 81 is particularlyuseful in conjunction with the device 50 as depicted in FIG. 10. Also,the vaginal applicator 81 is particularly well suited for use when thecopper ion treatments are in the form of either lotion, cream or gel.The vaginal applicator 81 comprises a hollow barrel 83 and a plunger 85slidably mounted in the hollow barrel 83. The barrel 83 has an openforward end defining a discharge opening 89 and has a rearward end wallthrough which a stem 91 of the plunger passes. The stem 91 is attachedat one end thereof to an internal flange 93 disposed within the barrelin close, sealing relation therewith. The plunger has a finger flange 95attached to an opposite end of the stem 91 that is disposed external ofthe barrel 83, the flange 95 being engageable with a finger or fingersof a hand in order to selectively depress and withdraw the plunger 85relative to the barrel 83. For use with the device 50, the forward endof the barrel 83 is provided with an internal thread 97 to threadedlyengage with the external thread 55 on the neck 56 of the tube 52.

FIG. 10 illustrates the vaginal applicator 81 being filled with thecopper ion treatment from the tube 52 of the device 50. As seen in FIG.10, the cap 54 is removed from the neck 56 of the tube 52, and theforward end of the barrel 83 is threaded onto the neck 56 via threadedengagement of the threads 55 and 97. At this stage, the plunger 85 isfully withdrawn relative to the barrel 83 such that the Internal flange93 is in abutment with the rearward end well of the barrel 83. The tube52 is then squeezed using pressure from the fingers in order to dispensethe copper ion treatment, represented at 98, into the barrel 83 from theopen neck 56 of the tube 52. When the barrel 83 is sized for aparticular dosage of copper ion treatment, a sufficient amount of copperion treatment can be dispensed from the tube 52 to entirely fill thespace within the barrel 83 from the neck of the tube 56 to the internalflange 93 which is in abutment with the rearward end wall of the barrel.Alternatively, an indicia or other marking 99 can be provided on thebarrel 83 to indicate the point to which the barrel 83 should be filledwith copper ion treatment 98 from the tube 52. It is preferred thatfilling the space within the barrel from the neck of the tube to theinternal flange corresponds to a dose of 5 grams of the copper iontreatment. Once the barrel 83 has been filed with the appropriate amountof copper ion treatment 98, the barrel 83 is disengaged from the neck 56of the tube 52 by disengaging the thread 97 from the thread 55. In orderto dispense the copper ion treatment 98 from the applicator 81, thefinger flange 95 of the plunger 85 is depressed toward the barrel 83using a finger, thereby causing the internal flange 93 to push thecopper ion treatment 98 through the discharge opening 89 as the plunger85 is depressed relative to the barrel 83. When the finger flange 95meets the rearward end wall of the barrel 83, the copper ion treatment98 will be fully discharged from the applicator. It should beappreciated that the applicator 81 could be used in conjunction withother devices for supplying the copper ion treatments to the barrel 85.It should also be appreciated that the applicator 81 can be supplied foruse pre-filled with copper ion treatment 98, in which case the forwardend of the barrel would be provided with a removable cap or seal. Theapplicator 81 is particularly advantageous for supplying the copper iontreatments to the vagina. Accordingly, prior to depressing the plunger85 to discharge the copper ion treatment 98 from the barrel 83, theforward end of the barrel 83 would be introduced into the vagina untilthe rearward end of the barrel was located near the entrance to thevagina. Then, upon depressing the plunger 85, the copper ion treatment98 is discharged from the discharge opening 89 into the vagina.

Another type of applicator useful in applying the copper ion treatmentsto anatomical tissue is shown at 101 in FIG. 11. The applicator 101 isin the nature of a swab comprising a handle 103 and a body of absorbentmaterial 105 at an end of the handle 103. The applicator 101 can be usedin conjunction with a container or bottle containing a copper iontreatment, such as the device 40 of FIG. 4. Upon removal of the cap 44from the bottle 42 of the device 40, the handle 103 of the applicator101 can be grasped with a hand used to manipulate the applicator 101 inorder to dip the body of absorbent material 105 into the copper iontreatment within the bottle 42. The body of absorbent material 105 canthen be gently contacted with anatomical tissue to be treated therebycausing the copper ion treatment carried by the absorbent body 105 to bedeposited on the anatomical tissue to be treated. The applicator 101 isbest suited for applying copper ion treatments to localized areas of theskin, nails, ear canal, nostrils, mouth and throat. Of course, it shouldbe appreciated that swab applicators 101 can be provided in sealedpackages with the bodies of absorbent material 105 pre-supplied withcopper ion treatment.

Another type of carrier that can be used to deliver copper iontreatments to the vagina is a tampon. The tampon used can be acommercially available tampon or one similar thereto. The tampon can beone having an applicator including a barrel containing the absorbenttampon body and a plunger slidable within the barrel to dispose or ejectthe absorbent tampon body from an open forward end of the barrel oncethe forward end has been introduced in the vagina an appropriatedistance in a commonly known manner of tampon use. In this case, anappropriate amount of copper ion treatment can be supplied to theabsorbent tampon body via the open forward end of the barrel prior tointroduction of the applicator in the vagina and ejection of theabsorbent tampon body from the applicator into the vagina. Anothersuitable tampon can be one without an applicator, i.e. a digital tampon,where the absorbent tampon body is inserted in the vagina by pushing itwith the fingers. In this case, the appropriate amount of copper iontreatment is simply deposited on the absorbent tampon body prior to itsinsertion in the vagina. In both cases, unless the tampon is going to beinserted in the vagina immediately or soon after the absorbent tamponbody has been provided with the appropriate amount of copper iontreatment, the tampon should be stored in a sealed container or packageuntil the time of its use in order to avoid evaporation of the copperion treatment. It should be appreciated that tampon bodies to which thecopper ion treatment has been supplied can be provided in sealedcontainers or packages, with or without an applicator, as a ready-to-usecommercial product. Alternatively, the appropriate amount of copper iontreatment may be deposited by the user on the absorbent tampon bodies oftampons sold separately or in conjunction with the copper ion treatment.Preferably, the tampon bodies are supplied with an amount of copperion-containing solution in the range of 5 to 10 milliliters.

FIG. 12 illustrates a tampon 110 according to an aspect of the presentdisclosure including an applicator 111 having a hollow barrel 113 and ahollow plunger 115, an absorbent tampon body 118, to which theappropriate amount of copper ion treatment has been supplied, disposedin the barrel 113 with the string 120 of the tampon body extending froma rear end of the plunger 115. The plunger 115 is slidable within andtoward the banal 113 to push the tampon body 118 and eject it from anopen forward end 128 of the barrel. The forward end 128 of the barrel113 can be tapered to facilitate introduction and advancement in thevagina and can be provided with slits that expand as the tampon body 118passes therethrough. The tampon 110 is provided in an air-tightcontainer or bottle 122 having a removable cap or lid 124. In order touse the tampon 110, the lid 124 is removed from the bottle 122 and thetampon 110 is removed from the bottle. The tampon 110 is inserted in thevagina in a conventional manner of using tampons. More specifically, theapplicator 111 is held by grasping a finger grip 126 on the barrel 113,and the forward end 128 of the barrel is inserted in the vagina. Theapplicator 111 is advanced into the vagina until the fingers graspingthe finger grip 126 touch the entrance to the vagina. The plunger 115 isthen pushed into the barrel 113, thus causing the tampon body 118 to beejected from the forward end 128 of the barrel into the vagina. Theapplicator 111 is then withdrawn from the vagina and discarded, leavingthe tampon body 118 in place in the vagina. Once the tampon body 118 isin place in the vagina, the copper ion treatment carried by the tamponbody contacts the anatomical tissue of the vagina and leaks into thevaginal fluid normally present in the vagina. The tampon body 118 isremoved from the vagina at the appropriate time by grasping and pullingon the string 120. Examples of tampons according to an aspect of thepresent disclosure are described below in Examples 23 and 24.

Example 23

A tampon for delivering a copper ion treatment to the vagina is preparedby supplying 5 milliliters of a copper ion-containing solution to anabsorbent tampon body intended to be introduced into the vagina.

Example 24

A tampon for delivering a copper ion treatment to the vagina is preparedby supplying 10 milliliters of a copper ion-containing solution to anabsorbent tampon body intended to be introduced into the vagina.

The copper ion-containing solution used in Examples 23 and 24 is theaccordance with the method set forth in Example 1. However, it should beappreciated that tampons can be provided in which the tampon bodies aresupplied with the alternative copper ion-containing solutions or otherforms of the copper ion treatments.

Another type of carrier useful to deliver the copper ion treatments tothe vagina and rectum is a suppository. Suppositories are commonly usedin the vagina and rectum (anus) as a means for dispensing various activeingredients or medicaments. Suppositories are made in various shapesincluding oviform, globular, conical and bullet shapes, and in varioussizes. Suppositories typically weigh in the range of 1 to 5 grams.Suppositories can be solid bodies composed of a mixture of a suitablesuppository base material and the active ingredients or medicaments.Alternatively, suppositories can be made with a solid outer wall ofsuppository base material enclosing non-solid active ingredients ormedicaments. The suppository base materials used in suppositories allowthem to dissolve or melt when exposed to the moisture (body fluid) orheat (body temperature) found in the vagina or rectum (rectal or analcanal), thereby releasing the active ingredients or medicaments into thevagina or rectum. Suitable suppository base materials include oleaginous(fatty) base materials, including cocoa butter, theobroma oil andsynthetic triglycerides, or water soluble or miscible base materials,including glycerinated gelatin and polyethylene glycol (PEG) polymers.It is preferred that the base materials be non-toxic, non-irritating,inert, and biocompatible. Suppositories suitable for use in an aspect ofthe present disclosure can be prepared in various ways according toconventional methods for preparing suppositories including compressionmolding and fusion molding. Suppositories for use as vaginal and rectalsuppositories according to an aspect of the present disclosure arepreferably made in two different sizes, i.e. a suppository weighing 3grams and a suppository weighing 5 grams, to accommodate different sizesof vaginal and rectal anatomy. Each size suppository can be made indifferent strengths based on the percentage by weight of the activeingredient. i.e. the copper ion treatment, relative to the total weightof the suppository. Preferably, the amount of copper ion-containingsolution in the suppository is in the range of 5% to 30% of the totalweight of the suppository. The suppositories are preferably formed inplastic molds and can be stored at room temperature. The suppositorieswill be effective against the body condition being treated when the onlyactive ingredient contained in the vaginal and rectal suppositories isthe copper ion treatment. However, the vaginal and rectal suppositoriescould contain additional ingredients that are inactive with respect tothe underlying condition or conditions being treated, such aspreservatives, penetrating additives, bioadhesives and stability aids.The suppositories may be inserted in the vagina and rectum using thefingers, or the suppositories may be provided with applicators tofacilitate insertion thereof in the vagina and rectum. Examples ofvaginal and rectal suppositories according to an aspect of the presentdisclosure are set forth in Examples 25-32, which utilize the copperion-containing solution of Example 1. However, the alternative copperion-containing solutions could be used in Examples 25-32.

Example 25

A suppository base material is combined with an appropriate amount ofcopper ion-containing solution and is molded into a suppository forvaginal or rectal use having a total weight of 3 grams, wherein thecopper ion-containing solution constitutes 5 percent of the total weightof the suppository.

Example 26

A suppository base material is combined with an appropriate amount ofcopper ion-containing solution and is molded into a suppository forvaginal or rectal use having a total weight of 3 grams, wherein thecopper ion-containing solution constitutes 10 percent of the totalweight of the suppository.

Example 27

A suppository base material is combined with an appropriate amount ofcopper ion-containing solution and is molded into a suppository forvaginal or rectal use having a total weight of 3 grams, wherein thecopper ion-containing solution constitutes 20 percent of the totalweight of the suppository.

Example 28

A suppository base material is combined with an appropriate amount ofcopper ion-containing solution and is molded into a suppository forvaginal or rectal use having a total weight of 3 grams, wherein thecopper ion-containing solution constitutes 30 percent of the totalweight of the suppository.

Example 29

A suppository base material is combined with an appropriate amount ofcopper ion-containing solution and is molded into a suppository forvaginal or rectal use having a total weight of 5 grams, wherein thecopper ion-containing solution constitutes 5 percent of the total weightof the suppository.

Example 30

A suppository base material is combined with an appropriate amount ofcopper ion-containing solution and is molded into a suppository forvaginal or rectal use having a total weight of 5 grams, wherein thecopper ion-containing solution constitutes 10 percent of the totalweight of the suppository.

Example 31

A suppository base material is combined with an appropriate amount ofcopper ion-containing solution and is molded into a suppository forvaginal or rectal use having a total weight of 5 grams, wherein thecopper ion-containing solution constitutes 20 percent of the totalweight of the suppository.

Example 32

A suppository base material is combined with an appropriate amount ofcopper ion-containing solution and is molded into a suppository forvaginal or rectal use having a total weight of 5 grams, wherein thecopper ion-containing solution constitutes 30 percent of the totalweight of the suppository.

FIG. 13 illustrates a strip 131 of interconnected packages or pods 132,each enclosing a vaginal or rectal suppository 130 containing a copperion treatment. The pods 132 are separated from each other by aperforation line 133 allowing the pods 132 to be detached from eachother by tearing along the perforation lines 133 as depicted in FIG. 13.Each pod 132 has front and rear walls 135 between which a suppository130 is retained. The front and rear walls 135 are sealed to one anotheralong their peripheral edges. As shown in FIG. 14, each pod 132 isprovided with a pair of finger tabs 134 respectively attached to thefront and rear walls 135, the finger tabs 134 being capable of beingpulled in opposite directions using the fingers to separate the opposedwalls 135 and thereby release the suppository 130 contained therein.

FIG. 15 illustrates an applicator 181 suitable for use in delivering asuppository 130 to the vagina or rectum. The applicator 181 is similarto the applicator 81 but does not have an internal thread at the forwardend of the barrel 183. In addition, the plunger 186 of the applicator181 has two internal flanges 193 a and 193 b within the barrel 183, theflange 193 a controlling the distance that the plunger can be withdrawnrelative to the barrel and the flange 193 b serving to eject thesuppository from the barrel when the plunger is depressed the fullamount. In use, a suppository 130 is manually positioned in the openforward end of the barrel 183 as illustrated in FIG. 15. The openforward end of the barrel 183 is preferably sized to retain thesuppository 130 in position without being overly snug or tight. Theplunger 185 is withdrawn the full amount relative to the barrel 183,which coincides with abutment of internal flange 193 a with the rearwardend wall of the barrel 183. The forward end of the barrel 183 holdingthe suppository is then introduced in the vagina or rectal (anal) canal,and the applicator 181 is gently pushed into the vagina or rectal canaluntil the fingers holding the rearward end of the barrel 183 areadjacent or touch the entrance to the vagina or rectal canal. The fingerflange 195 is then depressed to push the plunger 185 toward and into thebarrel 183 as shown by the arrow in FIG. 15, thus causing the flange 193b to engage the suppository 130 and eject it from the forward end of thebarrel into the vagina or rectal canal. The applicator 181 is thenremoved from the vagina or rectal canal, leaving the suppository in thevagina or rectal canal. The suppository will melt or dissolve in thevagina or rectal canal such that the copper ion treatment is released tocontact anatomical tissue of the vagina or rectal canal and to minglewith body fluid present in the vagina or rectal canal.

Another type of carrier that can be used to deliver the copper iontreatments to anatomical tissue is a body wipe. FIG. 16 illustrates abody wipe 200 contained in a sealed package 202 having front and rearwalls 203. The body wipe 200 comprises a thin sheet of material disposedin a folded condition when retained between the front and rear walls203, which are sealed along their peripheral edges. The body wipe 200enclosed between the front and rear walls 203 contains a wet or moistcopper ion treatment. The front and rear walls 203 may be grasped by thefingers at corresponding corners thereof and pulled in oppositedirections similar to the pods 132 in order to separate the front andrear walls 203 and thereby allow the body wipe 200 to be removed fromthe package 202. FIG. 16 shows the package 202 in a partially opencondition in which corresponding corner sections of the front and rearwalls 203 have been peeled away from one another thereby providingaccess to the body wipe 200. Upon removal from the package 202, the bodywipe 200 can be unfolded to its full size, which is substantially largerthan its size in the folded condition, and can be used to wipeanatomical tissue to be treated causing the copper ion treatment to betransferred to the anatomical tissue. The body wipe 200 is advantageousfor applying the copper ion treatments to the skin and the externalgenital and rectal areas.

Another type of carrier for the copper ion treatments is a wounddressing, such as a band aid, gauze pad or similar device. Such carrierscan be selected from products that are commercially available forremovable application to the skin to temporarily cover and protect anaffected area of the skin. FIG. 17 depicts a carrier in the nature of awound dressing 300 having a surface 301 for being placed in contact withthe skin. The surface 301 includes a protective surface 302 for beingpositioned over a wound, and an adhesive border surrounding the surface302. In use, a copper ion treatment, such as the copper ion-containingsolution in original form, can be liberally sprayed onto the surface 302of the carrier that is applied adjacent or in contact with the skin.Then, when the surface 302 of the carrier is applied adjacent or incontact with the skin and the carrier is left in place on the skin for aperiod of time, the copper ions contact or are transferred to the skinand provide the therapeutic effects described above. Of course, it wouldbe possible to provide carriers of this type in sealed packages in whichthe carriers are pre-supplied or pre-treated with the copper iontreatment similar to the body wipe 200.

A further type of carrier for the copper ion treatments is a skin patch,such as a dermal patch or a transdermal patch, represented at 400 inFIG. 18. The skin patch 400 has a drug delivery surface 401 containingthe copper ion treatment surrounded by an adhesive border 402. The patchis applied to the skin and left in place for a period of time with thedrug delivery surface in contact with the skin, causing the copper ionsto diffuse through the skin where they can act locally or penetrate thecapillaries for broader systemic effects. Examples of suitabletransdermal patches are the transdermal and microneedle 3M Drug DeliverySystems manufactured by 3M Corporation.

An additional type of carrier for the copper ion treatments is suturematerial, represented at 500 in FIG. 19, used by medical professionalsto close or suture external or internal incisions or wounds, i.e.“stitches.” Prior to using the suture material 500, which can beconventional suture material, the suture material can be soaked in thecopper ion-containing solution for a period of time in order to cover orsaturate the suture material with the solution. Suture material can alsobe stored in sealed packages containing the copper ion-containingsolution. Then, when the suture material 500 is used to create suturesor stitches in anatomical tissue T as seen in FIG. 19, the copper ionsin the solution contact the anatomical tissue and provide thetherapeutic effects previously described.

The copper ion-containing solution and the other forms of copper iontreatments described herein can be used on anatomical tissue in variousareas of the body including the genital-rectal areas (vagina, vulva,penis, scrotum, rectum (anus), rectal (anal) canal and surroundinganatomical areas), the oral-respiratory-otic areas (mouth, throat,airway, nostrils and ears) and the dermatological areas (skin and nails)of the body. The treatment effects provided by the copper ion treatmentsencompass treatment of active or existing disease and other undesirablebody conditions as well as the prevention of such diseases andconditions. The copper ion treatments are especially beneficial fortheir ability to kill or neutralize harmful or undesired pathogens andmicrobes including bacteria, viruses and fungi. Although the copper iontreatments am applied topically to anatomical tissue and have alocalized effect on diseases and undesirable body conditions affectingthe anatomical tissue, the copper ion treatments also have a broadersystemic effect on diseases and undesirable body conditions. The effectsrealized with the copper ion treatments include antibacterial,antimicrobial, antiseptic, antifungal, antiviral, anti-pathogenic,anti-inflammatory, spermicidal, neutralization of free radicals,promotion of healing and tissue repair, prevention of biofilm, andimmune-boosting effects. The diseases or conditions affecting thegenital-rectal areas that are treatable with the copper ion treatmentsinclude vaginitis, bacterial vaginosis, hemorrhoids, vaginal dryness,imbalances in vaginal pH, bacterial infections caused by gonorrhea,chlamydia, streptococcus and staphylococcus, protozoan infections causedby trichomonas, pelvic inflammatory disease, viral infections caused byherpes (I and II), HPV and HIV, fungal infections caused by yeastcandida, thrush and other fungi, exposure to sexually transmitteddiseases, and the risk of undesired pregnancy (contraception). Thediseases or conditions affecting the oral-respiratory-otic areas thatare treatable with the copper ion treatments include bacterialinfections caused by gonorrhea, chlamydia, streptococcus andstaphylococcus, protozoan infections caused by trichomonas, viralinfections caused by herpes (I and II), HPV and HIV, canker sores, mouthsores, mouth ulcers, colds, sinusitis, rhinosinusitis, sore throat,nasal discharge, congestion, runny nose, bronchitis, allergies, asthma,tonsillitis, wheezing, sneezing, ear infections, earache, pressure inthe ears, cough, hoarseness, laryngitis, sore gums, periodontal disease,bad breath and tooth decay. The diseases or conditions affecting thedermatological areas that are treatable with the copper ion treatmentsinclude bacterial infections caused by staphylococcus, streptococcus,enterobacter, E. coli and pseudomonas, viral infections caused byshingles and the associated postherpetic neuralgia (PHN) (a chronic,painful condition that can follow shingles), herpes (I and II) and HPV,fungal infections such as athlete's foot, ringworm and toenail fungus,impetigo, rosacea, psoriasis, eczema, warts, sun/wind damage, dry skin,age spots, pigmentation, scarring, blisters, boils, cysts, pimples,cuts, scratches, burns, abrasions, splinters, insect bites and stings,animal bites and scratches, ulcers, loss of elasticity or collagen,wrinkles, sagging skin, acne, measles, chicken pox, and the presence ofpathogens and microbes on the skin that is an inevitable consequence ofdaily life. Based on the result of laboratory testing, it is expectedthat the copper ion treatments will kill bacteria causing bacterialvaginosis, gonorrhea and chlamydia, and the viruses responsible forherpes (I and II) and HIV at a kill rate of 99.99 percent in 6 hours.Accordingly, the copper ion treatments are sufficiently effective to“cure” the diseases and conditions described herein and to prevent theoccurrence or development of such diseases and conditions. Similarly,copper has been demonstrated as having the capability to kill or renderinactive staphylococcus, streptococcus, enterobacter, trichomonas, E.coli and pseudomonas. The copper ion treatments are highly effective attreating the various abnormal or undesired body conditions while beingsafe and non-toxic. In particular, copper toxicity is so rare that theWorld Health Organization (WHO) has determined that there is no need forsetting an upper threshold for the ingestion of copper. The copper iontreatments can thus be safely used without concern for overdosing orimproper use. Moreover, it is believed that, to date, no bacteria orother harmful microorganisms have been found to be capable of developinga resistance to copper, in contrast to the many bacteria and organismsthat have developed or are in the process of developing resistance toconventional antibiotics. The multi-target effects of copper makesbacterial resistance extremely unlikely as copper kills bacteria veryquickly and leaves almost no survivors. Consequently, there is neitherthe time for bacteria to “learn” how to resist the killing effect ofcopper or the possibility to pass on any knowledge to a significantpopulation of survivors. The copper ion treatments provide a degree ofefficacy and safety for treating a wide array of diseases and bodyconditions that far surpasses conventional pharmaceutical andnon-pharmaceutical products and drugs available for treating the sameconditions.

Example 33

Treatment of Osteoarthritis Associated Chronic Pain with 3VM1001 Cream

Study Design

This study was a double-blind, placebo-controlled, randomized study ofthe use of 2 g of 3VM1001 cream, applied thrice daily, for the treatmentof chronic pain associated with osteoarthritis of the knee compared tothe inactive vehicle as a placebo. The composition of 3VM1001 cream isprovided in Example 34. Subjects were randomized in a 1:1 ratio to oneof two treatment arms (a) treatment with 3VM1001 cream or (b) placebo(3VM1002). A total of 50 subjects were enrolled, out of which 40subjects were evaluable.

The treatment phase consisted of a total of 90 self-administeredtreatments for chronic pain with either 3VM1001 cream or placebo. Allsubjects were to have three (3) study visits: an initial Screening/Entry(Visit 1) which may have taken place on two days over a period of sevendays to allow for a knee radiograph to be taken and reviewed, a followup visit at Day 7 after commencement of treatment (Visit 2) and a finalvisit (Visit 3) at 30 days after the commencement of treatment. Visits 2and 3 may take place ±3 days from the due date.

The results from one of the two study sites are summarized below.

Statistical Methods

The primary efficacy endpoint was the change from baseline in thetime-averaged self-reported Visual Analog Scale (VAS) score. Secondaryendpoints included the following:

-   -   1. Change from baseline in the (VAS) score at Visits 2 and 3.    -   2. Change from baseline in the time-averaged self-reported WOMAC        (Western Ontario and McMaster Universities) Pain Subscale score.    -   3. The change in the Global Rating of Disease from Baseline        (Day 0) to Day 30.    -   4. The Patient Global Impression of Change from Baseline in        Osteoarthritis.    -   5. The change in Patient Global Assessment of Treatment        Satisfaction from baseline to the end of the study.    -   6. The use of rescue medication.

The time-averaged mean change from baseline in the VAS for each subjectwas calculated by first computing the area under the curve (AUC) of thechanges from baseline vs. study day curve using the trapezoidal rule.The AUC was then divided by the number of study days from the first tothe last observation. These time-averaged means were analyzed by aone-way analysis of covariance that included the effects of treatmentgroup and baseline VAS. Data from all study days (including those beyond30 days) were included in the calculation of the time-averaged means.The mean changes from baseline in the daily VAS scores were created byfirst imputing all missing data through Day 30 by carrying the lastvalue forward.

Change from baseline in the VAS score at Visits 2 and 3 were eachanalyzed by a one-way analysis of covariance that included the effectsof treatment group and baseline VAS.

Change from baseline in the WOMAC Pain Subscale score at Visits 2 and 3were each analyzed by a one-way analysis of covariance that included theeffects of treatment group and baseline score. Time-averaged meanchanges from baseline and daily mean graphs were done as described abovefor self-reported VAS scores.

The change in the Global Rating of Disease from Baseline (Day 0) to Day30 was analyzed by the Cochran-Mantel-Haenszel procedure by assigninguniform scores (0-4) to each of the ordered outcomes of the 5-pointscale, stratified by the baseline score.

The Patient Global Impression of Change from Baseline in OsteoarthritisPain was analyzed by the Cochran-Mantel-Haenszel procedure by assigninguniform scores (0-6) to each of the ordered outcomes of the 7-pointscale.

The change in Patient Global Assessment of Treatment Satisfaction frombaseline to the end of the study was analyzed by theCochran-Mantel-Haenszel procedure by assigning uniform scores (0-4) toeach of the ordered outcomes of the 5-point scale.

The use of rescue medication was analyzed by counting the number of dayseach subject took one or more doses of rescue medication. Subjects whoterminated prematurely or did not have exactly 30 diary days had theirnumber of days with rescue medication normalized to 30 days by dividingthe number of days they took a rescue medication by the number of daysthey had diary data and multiplying by 30. These data were analyzed by atwo-sample t test.

The primary and all secondary analyses were two-sided and tested at asignificance level of 5%.

Results

Table 1 summarizes demographic data for the two treatment groups.Demographically, the two groups were comparable.

TABLE 1 Demographic Summary 3VM1001 Placebo (N = 11) (N = 12) Age N 9 12Mean 58.1 61.9 Range 49-73 52-74 Sex Males: n (%) 6 (54.5%) 7 (58.3%)Females: n (%) 5 (45.5%) 5 (41.7%) Race Black: n (%) 6 (54.5%) 4 (33.3%)Caucasian: n (%) 5 (45.5%) 8 (66.7%)

Table 2 summarizes the time-averaged changes from baseline I the VAS andthe WOMAC scores. Mean improvements over placebo were 16.2 and 3.1 forthe VAS and WOMAC, respectively.

TABLE 2 Mean Time-Averaged Changes From Baseline in Daily Diary ScoresVAS WOMAC Total 3VM1001 Placebo 3VM1001 Placebo Baseline Mean 69.6 65.616.4 16.4 Changes N 10 12 10 12 Mean¹ −26.1 −9.9 −4.47 −1.37 Difference(95% −16.2 (−36.6 to 4.2) −3.10 (−6.48 to 0.28) CI) P-Value 0.113 0.011¹Adjusted for baseline

Mean changes from baseline over time for the VAS and WOMAC are shown inFIGS. 20 and 21, respectively. Trends favoring 3VM1001 are seenthroughout the entire 30 days of treatment.

Table 3 summarizes the changes from baseline in the VAS scores at Days 7and 30. Mean improvements over placebo were 22.8 and 13.1 at Days 7 and30, respectively.

TABLE 3 VAS Scores at Days 7 and 30 Day 7 Day 30 3VM1001 Placebo 3VM1001Placebo Baseline Mean 67.8 65.6 69.6 65.6 Changes N 11 12 10 12 Mean¹−28.6 −5.8 −31.0 −17.9 Difference (95% −22.8 (−45.1 to −0.6) −13.1(−36.0 to 9.7) CI) P-Value 0.045 0.24 ¹Adjusted for baseline

Table 4 summarizes the changes from baseline in the WOMAC scores at Days7 and 30. Mean improvements over placebo were 5.4 and 2.4 at Days 7 and30, respectively.

TABLE 4 WOMAC Total Scores at Day 7 and 30 Day 7 Day 30 3VM1001 Placebo3VM1001 Placebo Baseline Mean 16.3 16.4 16.4 16.2 Changes N 11 12 10 11Mean¹ −5.57 −0.14 −5.94 −3.51 Difference (95% −5.43 (−9.27 to −1.58)−2.43 (−6.96 to 1.84) CI) P-Value 0.008 0.25 ¹Adjusted for baseline

Table 5 summarizes the satisfaction with the current treatment; Table 6summarizes the improvement with treatment; and Table 7 summarizes theglobal rating of disease. In each, the 3VM1001 showed consistentlyhigher scores throughout treatment.

TABLE 5 Satisfaction With Current Treatment Day 7 Day 30 3VM1001 Placebo3VM1001 Placebo Very 0 0 0 0 Dissatisfied Dissatisfied 1 4 3 2 NoPreference 3 3 1 2 Satisfied 2 4 1 6 Very Satisfied 5 1 5 2 P-Value0.075 0.79

TABLE 6 Improvement With Treatment Day 7 Day 30 3VM1001 Placebo 3VM1001Placebo Very much 0 0 3 2 improved Much improved 3 2 1 0 Improved 5 4 25 No change 3 4 4 4 Worse 0 0 0 0 Much worse 0 1 0 1 Very much 0 1 0 0worse P-Value 0.15 0.34

TABLE 7 Global Rating of Disease Baseline Day 7 Day 30 Pla- Pla- Pla-3VM1001 cebo 3VM1001 cebo 3VM1001 cebo Excellent 0 0 1 0 0 0 Very good 00 1 1 3 2 Good 1 0 2 0 4 2 Fair 7 7 4 6 1 7 Poor 4 5 3 5 2 1 P-value0.32 0.55

Table 8 summarizes the use of rescue medication. Thirty percent of thesubjects who received 3VM1001 took at least one dose of rescuemedication, compared to 50% of placebo subjects.

TABLE 8 Use of Rescue Medication 3VM1001 Placebo P-Value N 10 12Subjects who took at 3 (30%) 6 (50%) least one dose: n (%) Mean 4.2 4.40.95¹ Range 0-26.5 0-22.9 Median 0 0.5 0.51² ¹Two sample t test²Wilcoxon Rank Sum test

Table 9 summarizes adverse events. All events were rated as mild and allwere rated remote or unrelated by the investigator, except for headache,which was not rated for causality. No action was taken for any adverseevent, except the bacterial skin infection which appeared to be theresult of a sports injury not the 3VM1001 cream, and which resulted inthe patient terminating from the study.

TABLE 9 Adverse Event Summary 3VM1001 Placebo (N = 11) (N = 12) AdverseEvent n (%) n (%) Bacterial skin infection-R knee   1 (9.1%) 0 (0%)  Cold symptoms 0 (0%) 1 (8.3%) Headache 0 (0%) 1 (8.3%) Minimalerythema-Left Knee   1 (9.1%) 0 (0%)   Stomach Virus 0 (0%) 1 (8.3%)Tooth Pain 0 (0%) 1 (8.3%)

Example 34

Preparation of the Copper Ion Bulk Suspension

A copper-containing suspension was created by incubating 16 copperstrips (3.625 inches×2.25 inches×0.3 inches) in 2 L of 0.9% sodiumchloride buffered to approximately pH 5 by the addition of 0.016 gsodium phosphate monobasic anhydrous. The copper strips were separatedby stainless steel rods as shown in FIG. 22. The 0.9% sodium chloridesolution was placed into a closed borosilicate glass container in anoven heated to 37° C. and the copper strips and stainless steel rods (6rods for every 8 copper strips) were placed into a glass dish and heatedto 37° C. in the same oven. Once the sodium chloride solution reached atemperature of 37° C., the copper strips were placed into the salinesolution and allowed to incubate for 24 hours±30 minutes. The copperstrips and stainless steel rods were subsequently removed (FIG. 23), andthe remaining suspension was measured and collected into clean glasscontainers for immediate use, as shown in FIGS. 24-25. As shown in FIGS.23-25, precipitated copper salts form a sediment on the bottom of thecontainer. The total measured volume of bulk suspension, including theprecipitate was 32 oz.

Composition of the 3VM1001 Cream

This example provides an analysis of three of the 3VM1001 products: thebulk suspension used in the production of the 3VM1001 cream; a similarbulk suspension manufactured without the use of sodium phosphate, andthe 3VM1001 cream itself. The bulk suspension is a combination of aliquid phase and a solid phase. If left to stand, the solid phase willform a precipitate at the bottom of the bulk container. The objective,in part, of the analyses performed, was to assess the amount of copperfound in the liquid phase of the bulk suspension and the cream.

TABLE 10 Copper Composition of Bulk Suspension and 3VM1001 Cream Liquidphase Cu in Liquid Solid Phase Cu in Solid Test Article Compositionphase Composition Phase Bulk Sodium Below limit of Copper   37 μg/mLsuspension chloride detection phosphate; with (500 ppb) copper phosphatehydroxide Bulk Sodium 0.94 μg/mL Copper 9.99 μg/mL suspension chloride,hydroxide without copper phosphate chloride Cream 11.5 μg/mL  1.7 μg/mL

Table 10 shows that the solubility of the copper in the liquid phase bymore than 20-fold in the cream, compared to the bulk suspension. Cu isprimarily present in the liquid phase of the cream at 11.5 μg/mL,compared to 500 ppb (0.5 m/mL) for the bulk suspension with phosphate.Thus, the amount of copper present in the liquid phase is substantiallyenhanced in the 3VM1001 cream compared to the bulk suspension. Thisenhanced solubility was surprising and unexpected. Because dissolvedcopper is expected to have substantially greater bioavailability than asolid precipitate, this finding provides a rationale for the therapeuticeffect of the 3VM1001 cream.

To prepare the 3VM1001 cream, the bulk suspension is combined with acream base, such as VersaBase. Unless otherwise noted, the 3VM1001 creamcomprises 30% bulk suspension. More dilute creams with a lowerpercentage of bulk suspension and correspondingly higher percentage ofcream base were also prepared and tested, such as 3VM1001 20% (20% bulksuspension), 3VM1001 10% (10% bulk suspension), and 3VM1001 5% (5% bulksuspension). The composition of VersaBase is shown in Table 11, below.

The use of phosphate provides for a greater total copper concentrationin the precipitate (37 μg/mL compared to about 10 μg/mL in the phosphatefree bulk). See Table 10. Use of the phosphate bulk at a 30%concentration in the cream (which would be expected to produce a finalconcentration of about 11 μg/mL [30% of 37 μg/mL]) produces a coppercream product at a concentration of 11.5 μg/mL in the liquid phase.

TABLE 11 VersaBase Cream Quantitative Composition INCI Name (ChemicalName) % Trade Name Manufacturer Water 71.08% N/A N/A Emulsifying Wax NF11.00% Polawax NF-PA-(MH) Croda Inc. Ethylhexyl Stearate  8.00% LexolEHS Inolex Inc./Nexeo Cyclopentasiloxane  5.00% Xiameter ® PMX-0245Xiameter ® from Dow Cyclopentasiloxane Corning/Univar USA Sorbitol USPFCC  4.00% Sorbo ® Sorbitol Solution Ingredion/Univar USP/FCC ChicagoTocopheryl Acetate USP  0.50% DL-A-Tocopheryl Acetate DSM NutritionalProducts Aloe Barbadensis Leaf Juice  0.20% Aloe Vera Gel Freeze DriedAloe Vera of California Powder Powder 200:1 Extract- Inc. MicronizedDisodium EDTA USP FCC  0.18% Versene ™ NA Chelating Dow Chemical JECFAAgent Company/Univar USA Methylchloroisothiazolinone  0.04% Kathon ™ CGPreservative Rohm and Haas Methylisothiazolinone Chemicals LLCComposition of the LUXSOL Gel

To prepare a gel for use in the present disclosure, the bulk suspensionis combined with a gel base, such as VersaBase gel. The VersaBase gelconsists of the following ingredients:

-   -   Water    -   Ammonium Acryloyldimethyltaurate/VP Copolymer    -   Aloe Barbadensis Leaf Juice Powder    -   Allantoin    -   Disodium EDTA    -   Methylchloroisothiazolinone    -   Methylisothiazolinone

Unless otherwise noted, the LUXSOL gel comprises 30% bulk suspension.More dilute creams with a lower percentage of bulk suspension andcorrespondingly higher percentage of gel base were also prepared andtested, such as LUXSOL gel 20% (20% bulk suspension), LUXSOL gel % (10%bulk suspension), and LUXSOL gel 5% (5% bulk suspension).

Composition of the LUXSOL Suppository

To prepare the suppositories, the bulk suspension is combined with asuppository base comprising hydrogenated vegetable oil and PEG-8distearate.

Unless otherwise noted, the LUXSOL Suppository comprises 30% bulksuspension. More dilute suppositories with a lower percentage of bulksuspension and correspondingly higher percentage of suppository basewere also prepared and tested, such as LUXSOL Suppository 20% (20% bulksuspension), LUXSOL Suppository % (10% bulk suspension), and LUXSOLSuppository 5% (5% bulk suspension).

Example 35

The systemic and dermal toxicity and toxicokinetics of 3VM1001 creamwere evaluated following 30 days of 4-times daily topical administrationto Sprague Dawley rats, followed by a 2-week recovery period.

The objective of this study was to evaluate the systemic and dermaltoxicity and toxicokinetics of the test article following 30 days of4-times daily topical administration to Sprague Dawley rats, followed bya 2-week recovery period.

A total of 92 rats (46 males and 46 females) were randomized into 2treatment groups, including a vehicle control group (Group 1) and onetest article group (Group 2). Each group included a toxicity portionwith 2 cohorts (main and recovery) and a toxicokinetic (TK) portion.Animals received a topical administration of either vehicle cream(Group 1) or test cream (3VM1001 cream—Group 2) 4 times daily for 30consecutive days. Blood samples for TK analysis were collected on studyDay 1 (1 time point for control group and 6 time points for test group)and study Day 30 (1 time point for control group and 7 time points fortest group) from TK animals. Main study animals (10animals/gender/group) were euthanized on Day 31 and recovery animals (5animals/gender/group) were euthanized on Day 44 following a 2-weekperiod without treatment.

TABLE 12 No. of Animals/Sex Treatment Dose No. of Target Calculated(Recovery) (Cu conc. Amount ^(b) Daily Dose Level ^(c) Dose Level ^(d)Group Main TK as μg/mL) (mL/kg/dose) Doses (μg Cu/kg/day) (μg Cu/kg/day)1 10 (5) 3 + 1 3VM1002 0.33 4 0 0 (Vehicle) Vehicle Cream (0) 2 10 (5)9 + 1 3VM1001 0.33 4 14.4 18-20 Cream (12) ^(a) Note: The actual densityof test article was determined to be 1 g of cream = ~1.1 mL instead of 1mL as claimed; The actual dose level was calculated based on theprovided CoAs (concentration: 17 μg copper/g at predose and 15 μgcopper/g at post dose). ^(a) Nominal copper concentration. ^(b) Doseamount was increased from 0.3 mL/kg/dose to 0.33 mL/kg/dose (ProtocolAmendment 2). ^(c) Target dose level (μg Cu/kg/day) = 3.6 (μgCu/kg/dose) × 4 (times/day). ^(d) See Table 6 for an explanation.

All animals were dosed appropriately during the study. There were nounscheduled deaths or significant moribundity for any animal. There wereno findings during physical examinations, clinical observations or dosesite Draize scoring that indicated an adverse effect of test articleexposure. Animals consumed food normally each day, and gained weightduring the study, without significant differences in body weight betweengroups at any time point. Between-group differences in clinicalpathology parameters (hematology, serum chemistry) were of lowmagnitude, and consistent with normal biologic variation. There were noimportant differences in organ weights (only kidney weight higher inmale recovery animals), and no gross or microscopic pathology findingsthat were attributable to test article exposure.

The TK results indicated that there was no Cu absorption or accumulationafter 30 consecutive days of four times daily topical administration of3VM1001 cream. The quantifiable serum Cu concentrations in Group 23VM1001 cream (test) animals were similar to or less than those of Group1 3VM1002 cream (vehicle control). 3VM1002 has the same composition as3VM1001, except that it lacks copper ions

In conclusion, the no observable effect level for 3VM1001 cream appliedtopically to Sprague Dawley rats four times daily for 30 consecutivedays is greater than or equal to 18 μg copper/kg/day.

Example 36

The objective of this study was to evaluate the systemic and dermaltoxicity and toxicokinetics of 3VM1001 cream following topicaladministration to Hanford minipigs, followed by a 2-week recoveryperiod.

Two groups of miniature swine, each containing 12 animals (6 animals pergender) were successfully treated with either vehicle control (3VM1002cream—Group 1) or the test article (3VM1001 cream (containing copper,Cu)—Group 2), administered topically 4 times daily for 30 consecutivedays. Two animals per gender per group were followed for an additional 2weeks without treatment. Animals were evaluated for signs of toxicitythrough physical examinations, clinical observations, body weight andbody weight change, dose site Draize scoring, clinical pathology(hematology, coagulation, serum chemistry and urinalysis),electrocardiography, ophthalmology, organ weight and histopathology.Toxicokinetic characteristics were assessed on study Day 1 and Day 30.

TABLE 13 No. of Animals Treatment Dose No. of Target Calculated(Recovery) (Cu conc. Amount^(b) Daily Dose Level ^(c) Dose Level ^(d)Group Male Female as μg/g) (mL/kg/dose) Doses (μg Cu/kg/day) (μgCu/kg/day) 1 4 (2) 4 (2) 3VM1002 0.33 4 0 0 (Vehicle) Vehicle Cream (0)2 4 (2) 4 (2) 3VM1001 0.33 4 14.4 18-20 Cream (12)^(a) Note: The actualdensity of test article was determined to be 1 g of cream = 1.1 mLinstead of claimed as 1 g of cream = 1 mL; The actual dose level wascalculated based on the provided CoAs (concentration: 17 μg copper/g atpredose and 15 μg copper/g at post dose). ^(a)Nominal copperconcentration. ^(b)Dose amount was increased from 0.3 mL/kg/dose to 0.33mL/kg/dose on Day 3 (Protocol Amendment 2, Appendix I). ^(c) Target doselevel (ug Cu/kg/day) = 3.6 (μg Cu/kg/dose) × 4 (times/day). ^(d) SeeTable 6 for an explanation.

All animals were dosed appropriately during the study. There were nounscheduled deaths or significant moribundity for any animal. There wereno findings during physical examinations, clinical observations or dosesite Draize scoring that indicated an adverse effect of test articleexposure. Animals generally consumed all food offered each day, andgained weight during the study, without significant differences in bodyweight between groups at any time point. There were no test articleassociated findings with respect to electrocardiography or ophthalmologyassessments. Between-group differences in clinical pathology parameters(hematology, coagulation, serum chemistry and urinalysis) were of lowmagnitude, and consistent with normal biologic variation. There were noimportant differences in organ weights, and no gross or microscopicpathology findings that were attributable to test article exposure.

Serum Cu concentrations (TK) were determined for control animals (1 hourpostdose), 7 time points in test animals on study Day 1 and Day 30 andon termination days on 31 and 44. The TK results indicated that therewas no Cu absorption or accumulation after 30 consecutive days of fourtimes daily topical administration of 3VM1001 cream. The quantifiableserum Cu concentrations in Group 2 3VM1001 cream (test) animals weresimilar to or less than those of Group 1 3VM1002 cream (vehiclecontrol).

In conclusion, the no observable effect level for 3VM1001 creamadministered topically to miniature swine four times daily for 30consecutive days is greater than or equal to 18 μg copper/kg/day.

Example 37

A suspension consisting of 46 μg/mL of copper in 0.9% normal saline with0.8 g/L NaPO₄ added for pH adjustment (referred to herein as 3VM1000)was evaluated for the potential to induce chromosome aberrations in HPBLduring short (3-hour) and long (22-hour) incubations with or without anexogenous metabolic activation system.

HPBL cultures were treated with the test article, positive control, orvehicle control in the presence and absence of an Aroclor™ 1254-inducedrat liver S9 microsomal fraction. The saline concentration in theculture medium was 10% v/v. 3VM1000 concentrations tested in therange-finding assay ranged from 1%-10% v/v in culture, up to the highestfeasible concentration dosing 10% of the provided solution. Precipitateswere observed at the end of treatment at 10% in each treatment. Based oncytotoxicity (i.e., reduction in mitotic index) observed in therange-finding assay, concentrations used during the chromosomeaberration assay ranged from 2%-10% v/v in culture.

The concentrations selected for evaluation of chromosome aberrations inthe aberration assay were based on precipitates and are as follows: a)3-hour treatment without metabolic activation, 4%, 6% (highestconcentration tested without precipitates), and 8% (lowest concentrationtested with precipitates); b) 22-hour treatment, 6%, 8% (highestconcentration tested without precipitates), and 10% (lowestconcentration tested with precipitates); and c) 3-hour treatment withactivation, 2%, 4% (highest concentration tested without precipitates),and 6% (lowest concentration tested with precipitates). These cultures,along with the vehicle and 1 concentration of positive control for eachtreatment condition, were analyzed for aberrations. Structuralchromosome aberrations were scored for each concentration from a totalof 300 metaphase cells (when possible) or ≥50 aberrant cells. Numericalaberrations were evaluated in 400 metaphase cells per concentration.

No statistically significant differences in the percent of cells withstructural chromosome aberrations or the percent of cells with greaterthan 1 aberration were noted under any assay condition. In addition,there was no statistically significant test article-related increase innumerical aberrations (polyploidy or endoreduplication) in any treatmentcompared to the vehicle controls. The data from the vehicle, negative,and positive controls demonstrated the validity and sensitivity of thistest system.

3VM1000 was considered negative for inducing structural aberrations inHPBL with or without metabolic activation under the conditions of thistest system. In addition, no statistically significant increases innumerical aberrations (polyploidy or endoreduplication) were observed in3VM1000-treated cultures.

Example 38

The objective of this study was to assess the potential of the testarticle to induce micronuclei in polychromatic erythrocytes (PCEs) inrat bone marrow following 3 consecutive days of treatment administeredby oral gavage. This assay evaluated compounds for in vivo clastogenicactivity and/or disruption of the mitotic apparatus.

3VM1000 in the vehicle (0.9% sodium chloride, USP) was administeredorally by gavage once daily for 3 consecutive days to 3 groups (Groups2-4) of Crl:CD(SD) rats. Dosage levels were 0.046, 0.153, and 0.46mg/kg/day for Groups 2, 3, and 4, respectively. A concurrent vehiclecontrol group (Group 1) received the vehicle on a comparable regimen. Apositive control group (Group 5) received a single oral dose of 60 mg/kgcyclophosphamide monohydrate (CPS) on study day 2, the day prior to thescheduled euthanasia. The dose volume was 10 mL/kg for all groups. Eachgroup consisted of 6 animals/sex. All animals were euthanized on studyday 3, at approximately 18-24 hours following dose administration forGroups 1-4 and at approximately 24 hours following dose administrationfor Group 5, and discarded following bone marrow collection.

All animals were observed twice daily for mortality and moribundity.Detailed physical examinations were performed and individual bodyweights were recorded weekly (±2 days) during acclimation, on the day ofrandomization, on study day 0 (prior to dosing), on study day 2 (lastday of dosing), and on the day of the scheduled euthanasia. Clinicalexaminations were performed at the time of dose administration and 1-2hours following dose administration. Individual food weights wererecorded weekly (±2 days) during acclimation, on the day ofrandomization, on study day 0, and on the day of the scheduledeuthanasia. Bone marrow collection for micronucleus evaluation wasperformed for 5 of 6 animals/sex/group at the scheduled euthanasia(study day 3). All animals were discarded without necropsy at thescheduled euthanasia. Bone marrow smears were prepared and the codedslides were counted for polychromatic, normochromatic, andmicronucleated polychromatic erythrocytes following the final bonemarrow sample collection on study day 3.

All animals survived to the scheduled euthanasia. There were no testarticle-related clinical observations or effects on body weights or foodconsumption. 3VM1000 did not produce an increase in the mean number ofmicronucleated polychromatic erythrocytes (MN-PCEs) compared to thevehicle control group. No bone marrow cytotoxicity (decreases in theratio of polychromatic to total erythrocytes, PCE:TE ratio) was noted inany test article-treated group. Therefore, 3VM1000 met the criteria fora negative response for bone marrow cytotoxicity and clastogenicityunder the conditions of this assay.

Based on the results of this study, oral administration of 3VM1000 oncedaily to Crl:CD(SD) rats for 3 consecutive days resulted in a negativeresponse for induction of bone marrow micronuclei at dosage levels up to0.46 mg/kg/day.

Example 39

The objective of this study was to determine the potential of 3VM1001cream to produce a skin sensitization reaction following dermal topicaladministrations (induction exposures) followed by a challenge dose toyoung adult guinea pigs.

This study was conducted with thirty-nine (39) healthy female youngadult guinea pigs. Twenty one (21) animals were administered with3VM1001 cream, seven (7) animals were administered with DNCB(dinitro-chloro-benzene) as positive controls and eleven (11) animalswere administered with 3VM1002 cream, the vehicle cream, as negativecontrols. There were two test phases (induction and challenge phase) inthe proposed experiment. In the induction phase (Day 1), each animal wastopically administered with either test or control substance on theflank area for 6±0.5 hours. The same procedure was performed three (3)times per week for three (3) consecutive weeks for the two controlgroups and the test group. For the challenge phase (Day 32), theuntreated flank areas of test and control animals were topicallyadministered with the appropriate amount of test or control substanceusing an occlusion patch for 6±0.5 hours. Dermal irritation was scoredat 24±2 and 48±2 hours post challenge phase patch removal.

No skin irritation was observed to be associated with administration ofthe test or control cream at either scoring time points (24 or 48hours).

In conclusion, the 3VM1001 cream did not cause skin sensitizationreaction under the conditions of this study.

Example 40

3VM1001 showed ≥99.99% antimicrobial activity against Streptococcusmutans in an in vitro test.

Organism Preparation

Stock cultures was transferred into appropriate growth media andsubcultured on solid media three times.

Inoculum Suspension Preparation and Determination of the MicrobialPopulation

The inoculum suspensions were enumerated in duplicate by standardmicrobiological procedures at the initiation and completion of testing.Appropriate dilutions were prepared and enumerated by standardmicrobiological procedures

-   -   To prepare the inoculum suspension from an agar plate, microbial        growth from the agar surface was washed with buffered phosphate        diluent.    -   10⁻¹, 10⁻², 10⁻³, 10⁻⁴, 10⁻⁵, 10⁻⁶, 10⁻⁷, 10⁻⁸, 10⁻⁹, 10⁻¹⁰        dilutions of the organism were prepared.    -   1.0 ml of each dilution was plated onto the growth media. The        plates were incubated at 37° C. for 48 hours aerobically.    -   The plates were then observed for growth after 48 hours        incubation.    -   Colonies were counted.

The inoculum suspension carrying a minimum of 10⁸ cfu/mL microbialpopulation was selected. The final inoculum suspension was well mixedprior to addition to test materials.

Procedure

Each concentration was tested in duplicate. Each recovery sample wasplated in duplicate. The microbial population inoculated was contained aminimum of 10⁶ cfu/mL. Before initiating the actual test, the sampleswere screened for sterility. All liquid containers were disinfected byswabbing thoroughly with 95% ethanol, rinsing with 95% ethanol, andair-drying inside biosafety hood. Ten gram of the test sample was addedto sterile glass tubes. 0.1 ml of organism suspensions were addeddirectly onto the test sample tube and control tube contained 10 ml ofsterile phosphate buffer. Tubes were vortexed thoroughly to mix theorganisms and placed at 37° C. in the incubator set at that temperaturefor the specified contact time.

After 1 hr and 6 hrs of incubation, 1 ml aliquots were removed and addedto 9 ml of sterile DE Neutralizing broth in tubes. Suspensions werevortexed and 10-fold serial dilutions were prepared. Aliquots of 1 mlfrom each dilution were plated in duplicate and plates were incubated at37° C. for 48 hours aerobically. Colonies were counted, and theconcentration of viable cells were calculated. Surviving Organisms wereidentified by growth on Columbia CNA agar. Organisms were identified bybiochemical tests (catalase negative, oxidase negative) and growth ofGram-positive cocci on Columbia CNA agar was detected by Gram staining.

Results

TABLE 14 3VM1001 Cream showed ≥99.99% antimicrobial activity againstStreptococcus mutans Concentration of Organism (CFU/ml) Exposure Repli-Streptococcus mutans ATCC# 25175 % Log Sample ID Time cate Cfu/mlAverage Reduction reduction Control 0 Hr A 88000000 99000000 9.4 × 10⁷ —— 110000000 B 87000000 89000000 91000000 3VM1000 1 Hr A 0 0 0 ≥99.99%7.99 30 ml 0 B 0 0 0 3VM1000 6 Hr A 0 0 0 ≥99.99% 7.99 30 ml 0 B 0 0 0Conclusion

3VM1001 showed ≥99.99% antimicrobial activity against Streptococcusmutans ATCC #25175 after 1 hour or 6 hours of contact time.

Example 41

3VM1001 cream showed ≥99.99% antimicrobial activity against Gardnerellavaginalis.

SUMMARY

The test material was brought into contact with a known population oforganisms for a specified exposure time at a specified temperature. Theactivity of the test material was monitored at specified exposure timesand the surviving organisms enumerated. The percent reduction, fromeither an initial population or test blank, is calculated.

Test Materials:

3VM1001, 5%, 10%, 20% or 30%. The cream was prepared according toExample 34 with 5%, 10%, 20% or 30% bulk suspension.

Test Method:

The procedure was the same as described in Example 40, except thatsurviving organisms were identified by: growth on chocolate agar, nogrowth on MacConkey agar, and biochemical tests (catalase negative,oxidase negative).

Results:

TABLE 15 3VM1001 cream showed ≥99.99% antimicrobial activity againstGardnerella vaginalis Concentration of Organism (CFU/mL) Exposure Repli-Gardnerella vaginalis ATCC# 49145 % Log Sample Id Time cate Cfu/mlAverage Reduction reduction Control 0 Hr A 1500000 1800000 2.1 × 10⁶ — —2100000 B 2000000 2400000 2800000 Cream 5% 6 Hr A 0 0 0 ≥99.99% 6.3 0 B0 0 0 Cream 10% 6 Hr A 0 0 0 ≥99.99% 6.3 0 B 0 0 0 Cream 20% 6 Hr A 0 00 ≥99.99% 6.3 0 B 0 0 0 Cream 30% 6 Hr A 0 0 0 ≥99.99% 6.3 0 B 0 0 0Conclusion:

3VM1001 cream at 5%, 10%, 20% and 30% showed ≥99.99% antimicrobialactivity against Gardnerella vaginalis ATCC #49145 at 6 hours of contacttime.

Example 42

The LUXSOL gel showed ≥99.99% antimicrobial activity against Gardnerellavaginalis.

Test Materials:

LUXSOL Gel 5%, Gel 10%, Gel 20%, Gel 30% The gel was prepared accordingto Example 34 with 5%, 10%, 20% or 30% bulk suspension.

Test Method:

The procedure was the same as described in Example 41.

Results:

TABLE 16 LUXSOL gel showed ≥99.99% antimicrobial activity againstGardnerella vaginalis. Concentration of Organism (CFU/mL) ExposureRepli- Gardnerella vaginalis ATCC# 49145 % Log Sample Id Time catedCfu/ml Average Reduction reduction Control 0 Hr A 1500000 1800000 2.1 ×10⁶ — — 2100000 B 2000000 2400000 2800000 Gel 5% 6 Hr A 0 0 0 ≥99.99%6.3 0 B 0 0 0 Gel 10% 6 Hr A 0 0 0 ≥99.99% 6.3 0 B 0 0 0 Gel 20% 6 Hr A0 0 0 ≥99.99% 6.3 0 B 0 0 Gel 30% 6 Hr A 0 0 0 ≥99.99% 6.3 0 B 0 0 0Conclusion:

LUXSOL Gel 5%, 10%, 20% and 30% each showed ≥99.99% antimicrobialactivity against Gardnerella vaginalis ATCC #49145 at 6 hours of contacttime.

Example 43

The LUXSOL suppositories showed >99.99% antimicrobial activity againstGardnerella vaginalis.

Test Materials:

LUXSOL Suppository 5%, 10%, 20%, and 30%. The LUXSOL suppositories wereprepared according to Example 34 with 5%, 10%, 20% or 30% of bulksuspension.

Test Conditions:

The procedure was the same as described in Example 41.

Results:

TABLE 17 LUXSOL suppositories showed >99.99% antimicrobial activityagainst Gardnerella vaginalis Concentration of Organism (CFU/mL)Exposure Repli- Gardnerella vaginalis ATCC# 49145 % Log Sample Id Timecate Cfu/ml Average Reduction reduction Control 0 Hr A 1500000 18000002.1 × 10⁶ — — 2100000 B 2000000 2400000 2800000 Suppository 5% 6 Hr A 00 0 ≥99.99% 6.3 0 B 0 0 0 Suppository 10% 6 Hr A 0 0 0 ≥99.99% 6.3 0 B 00 0 Suppository 20% 6 Hr A 0 0 0 ≥99.99% 6.3 0 B 0 0 0 Suppository 30% 6Hr A 0 0 0 ≥99.99% 6.3 0 B 0 0 0Conclusion:

LUXSOL suppositories comprising 5%, 10%, 20% or 30% of the coppersolution showed >99.99% antimicrobial activity against NeisseriaGonorrhoeae ATCC #49145 at 6 hours of contact time.

Example 44

3VM1001 cream showed ≥99.99% antimicrobial activity against Neisseriagonorrhoeae.

Test Materials:

3VM1001 Cream, prepared according to Example 34 with 30% bulksuspension.

Test Method:

The procedure was the same as described in Example 41.

Results:

TABLE 18 3VM1001 Cream showed ≥99.99% antimicrobial activity againstNeisseria gonorrhoeae ATCC# 49226 Concentration of Organism (CFU/mL)Exposure Repli- Neisseria gonorrhoeae ATCC# 49226 % Log Sample Id Timecate Cfu/ml Average Reduction reduction Control 0 Hr A 3700000 41000004.5 × 10⁶ — — 4500000 B 5600000 4900000 4200000 Cream 30% 6 Hr A 0 0 0≥99.9% 6.6 0 B 0 0 0Conclusion:

3VM10001 Cream showed ≥99.9% antimicrobial activity against Neisseriagonorrhoeae ATCC #49226 at 6 hours of contact time.

Example 45

The LUXSOL gel showed ≥99.99% antimicrobial activity against Neisseriagonorrhoeae.

Test Materials:

LUXSOL Gel 30%. The LUXSOL gel was prepared according to Example 34.

Test Method:

The procedure was the same as described in Example 41.

Results:

TABLE 19 The LUXSOL gel showed ≥99.99% antimicrobial activity againstNeisseria gonorrhoeae. Concentration of Organism (CFU/mL) ExposureRepli- Neisseria gonorrhoeae ATCC# 49226 % Log Sample Id Time cateCfu/ml Average Reduction reduction Control 0 Hr A 3700000 4100000 4.5 ×10⁶ — — 4500000 B 5600000 4900000 4200000 Gel 30% 6 Hr A 0 0 0 ≥99.99%6.6 0 B 0 0 0Conclusion:

LUXSOL gel showed ≥99.99% antimicrobial activity against Neisseriagonorrhoeae ATCC #49226 at 6 hours of contact time.

Example 46

The LUXSOL suppository showed >99.99% antimicrobial activity againstNeisseria gonorrhoeae.

Test Materials:

LUXSOL suppository. The suppository was prepared according to Example34.

Test Conditions:

The procedure was the same as described in Example 41.

Results:

TABLE 20 The LUXSOL suppository showed >99.99% antimicrobial activityagainst Neisseria gonorrhoeae Concentration of Organism (CFU/mL)Exposure Repli- Neisseria gonorrhoeae ATCC# 49226 % Log Sample Id Timecate Cfu/ml Average Reduction reduction Control 0 Hr A 3700000 41000004.5 × 10⁶ — — 4500000 B 5600000 4900000 4200000 Suppository 30% 6 Hr A 00 0 ≥99.99% 6.6 0 B 0 0 0Conclusion:

LUXSOL suppository showed ≥99.99% antimicrobial activity againstNeisseria gonorrhoeae ATCC #49226 at 6 hours of contact time.

Example 47

3VM1001 cream showed >99.99% antimicrobial activity against Mobiluncuscurtisii subsp. Curtisi

Test Materials:

3VM1001 cream, prepared according to Example 34.

Test Conditions:

The procedure was the same as described in Example 41.

Results:

TABLE 21 The 3VM1001 showed >99.99% antimicrobial activity againstMobiluncus curtisii subsp. Curtisii Concentration of Organism (CFU mL)Mobiluncus curtisii subsp. Curtisii Exposure Repli- NCTC 11656 (ATCC #35241) % Log Sample Id Time cate Cfu/ml Average Reduction reductionControl 0 Hr A 1510000 1355000 1.3 × 10⁶ — — 1200000 B 1700000 14000001100000 Cream 30% 6 Hr A 0 0 0 ≥99.99% 6.11 Lot# 0 04192013@9 B 0 0 0Conclusion:

3VM1001 cream showed ≥99.99% antimicrobial activity against Mobiluncuscurtisii subsp. Curtisii ATCC #35241 at 6 hours of contact time.

Example 48

3VM1001 cream showed >99.99% antimicrobial activity against Atopobiumvaginae.

Test Materials:

3VM1001 cream, prepared according to Example 34.

Test Conditions:

The procedure was the same as described in Example 41.

Results:

TABLE 22 3VM1001 Cream showed 99.99% antimicrobial activity againstAtopobium vaginae Exposure Repli- Concentration of Organism (CFU/mL) %Log Sample Id Time cate Cfu/ml Average Reduction reduction Control 0 HrA 160000000 160000000 1.68 × 10⁸ — — 162000000 B 173000000 175000000177000000 Atopobium 6 Hr A 2600 2500  2.7 × 10³ 99.99% 2.67 vaginae 2400ATCC# B 2800 2900 BAA-55 3000Conclusion:

3VM1001 Cream showed 99.99% antimicrobial activity against Atopobiumvaginae ATCC #BAA-55 at 6 hours of contact time.

Example 49

3VM1001 Cream showed 99.99% antimicrobial activity against Chlamydiatrachomatis. Chlamydia trachomatis (Serotype K) was exposed to 3VM1001Cream at 35-37° C. (36.0° C.) for 6 hrs. Complete inactivation ofChlamydia trachomatis (Serotype K) was demonstrated.

Example 50

3VM1001 Cream showed 99.99% antiviral activity against HumanImmunodeficiency Virus type 1 (HIV-1). HIV-1 was exposed to 3VM1001Cream at 35-37° C. (36.0° C.) for 6 hrs. Complete inactivation of thetest virus was demonstrated. A ≥99.99% reduction in viral titer wasdemonstrated. The log reduction in viral titer was ≥4.00 log₁₀.

Example 51

LUXSOL Gel showed 99.99% antiviral activity against HumanImmunodeficiency Virus type 1 (HIV-1). HIV-1 was exposed to LUXSOL Gelat 35-37° C. (36.0° C.) for 6 hrs. Complete inactivation of the testvirus was demonstrated. A ≥99.99% reduction in viral titer wasdemonstrated. The log reduction in viral titer was ≥4.00 log₁₀.

Example 52

Luxsol Suppository showed 99.99% antiviral activity against HumanImmunodeficiency Virus type 1 (HIV-1). HIV-1 was exposed to the LUXSOLsuppository according to Example 34 at 35-37° C. (36.0° C.) for 6 hrs.Complete inactivation of the test virus was demonstrated. A ≥99.99%reduction in viral titer was demonstrated. The log reduction in viraltiter was ≥4.00 log₁₀.

Example 53

3VM1001 cream showed 99.53% antimicrobial activity against Candidaalbicans.

-   TEST MATERIALS: 3VM1001 Cream, prepared according to Example 34 with    30% bulk suspension.    Test Method:

The procedure was the same as described in Example 41.

Results:

3VM1001 Cream 30% showed 99.53% antimicrobial activity against Candidaalbicans

Concentration of Organism (CFU/mL) Exposure Repli- Candida albicansATCC# 10231 % Log Sample Id Time cate Cfu/ml Average Reduction reductionControl 0 Hr A 27000000 29000000 2.6 × 10⁷ — — 31000000 B 1800000023000000 28000000 Cream 30% 6 Hr A 70000 80000 1.2 × 10⁵ 99.53% 2.3 Lot#90000 04192013@9 B 120000 160000 200000Conclusion:

3VM1001 showed 99.53% antimicrobial activity against Candida albicansATCC #10231 at 6 hours of contact time.

Example 54

An appropriate amount of copper ion-containing suspension, such as3VM1000, is combined with a toothpaste base material to form a copperion toothpaste in which the copper ion-containing solution constitutesin the range of 5 percent to 30 percent of the total weight of thecopper ion toothpaste.

The toothpaste base material can be a commercially available toothpasteincluding any of the toothpastes marketed and sold under the major brandnames. A toothpaste made in accordance with Example 54 is advantageousfor preventing biofilm (plaque), treating bad breath, sore gums, gumdisease and tooth decay when used on a daily basis in place of aperson's regular toothpaste.

Example 55

The 3VM1000 copper ion-containing suspension was used as a mouthwash toprevent biofilm formation (plaque) in two individuals. Specifically, onetablespoon of 3VM1000 was as a mouthwash once a day for one minute, overthe course of one year. Oral examinations every three months showed thatboth individuals were 99-100% plaque free throughout the course of thetreatment.

The invention claimed is:
 1. A pharmaceutically acceptable formulationfor use in treating a condition causing pain and/or swelling of a jointof a subject, the pharmaceutically acceptable formulation consisting of:(a) a carrier consisting of a liquid phase and a soluble phase, theliquid phase comprising about 5 μg/mL to about 15 μg/mL copper ions; and(b) a copper ion-containing suspension consisting of: (i) a salinesolution; (ii) one or more buffers; and (iii) copper ions, wherein thecopper ions are a result of: (A) placing a solid copper metal of 99.5%or greater copper content into the saline solution; (B) allowing thesolid copper metal to remain in the saline solution for a predeterminedperiod of time; and (C) removing the solid copper metal from the salinesolution, thereby disposing the copper ions in the saline solution. 2.The pharmaceutically acceptable formulation of claim 1, wherein thecondition is osteoarthritis.
 3. The pharmaceutically acceptableformulation of claim 1, wherein the joint is a knee, a hip, an elbow, ahand joint, a spine or a toe.
 4. The pharmaceutically acceptableformulation of claim 1, wherein the joint is a knee joint.
 5. Thepharmaceutically acceptable formulation of claim 1, wherein the subjectachieves a VAS score that is at least 15 units lower than a baseline VASscore.
 6. The pharmaceutically acceptable formulation of claim 5,wherein the subject achieves a VAS score that is at least 25 units lowerthan the baseline VAS score.
 7. The pharmaceutically acceptableformulation of claim 1, wherein the subject achieves a WOMAC score thatis at least 4 units lower than a baseline WOMAC score.
 8. Thepharmaceutically acceptable formulation of claim 1, wherein the carrierhaving a liquid phase is selected from the group consisting of a creambase, a lotion base, a gel base, and a foam base.
 9. Thepharmaceutically acceptable formulation of claim 8, wherein the carrieris a cream base.
 10. The pharmaceutically acceptable formulation ofclaim 9, wherein the cream base comprises water, emulsifying wax,ethylhexyl stearate, cyclopentasiloxane, sorbitol, tocopheryl acetate,aloe barbadensis leaf juice powder, disodium EDTA,methylchloroisothiazolinone, and methylisothiazolinone.
 11. Thepharmaceutically acceptable formulation of claim 1, wherein thepharmaceutically acceptable formulation comprises at least 10 μg/mLcopper ions in the liquid phase.
 12. The pharmaceutically acceptableformulation of claim 1, wherein the pharmaceutically acceptableformulation comprises about 11.5 μg/mL copper ions in the liquid phase.13. The pharmaceutically acceptable formulation of claim 1, wherein thepharmaceutically acceptable formulation comprises copper ions disposedin a solution as a result of leaching copper ions from a solid coppermetal, and wherein the solid copper metal consists of pure copper. 14.The pharmaceutically acceptable formulation of claim 13, wherein thepharmaceutically acceptable formulation consists of 5%, 10%, 20%, or 30%of the solution.
 15. A method of treating a condition that causes painand/or swelling of a joint comprising topically administering thepharmaceutically acceptable formulation of claim 1 1-3 times daily to ahuman in need of such treatment.
 16. The method of claim 15, wherein thecondition is osteoarthritis.
 17. The method of claim 15, wherein thejoint is a knee, a hip, an elbow, a hand joint, a spine or a toe. 18.The method of claim 17, wherein the joint is a knee joint.
 19. Themethod of claim 15, wherein the subject achieves a VAS score that is atleast 15 units lower than the baseline VAS score.
 20. The method ofclaim 19, wherein the subject achieves a VAS score that is at least 25units lower than the baseline VAS score.
 21. The method of claim 15,wherein the subject achieves a WOMAC score that is at least 4 unitslower than the baseline WOMAC score.
 22. The method of claim 15, whereinthe pharmaceutically acceptable formulation is a cream, lotion, gel or afoam.
 23. The method of claim 22, wherein the pharmaceuticallyacceptable formulation is a cream.
 24. The method of claim 23, whereinthe cream is 3VM1001.
 25. The method of claim 22, wherein thepharmaceutically acceptable formulation comprises at least 10 μg/mLcopper ion in the liquid phase.
 26. The method of claim 22, wherein thepharmaceutically acceptable formulation comprises about 11.5 μg/mLcopper ion in the liquid phase.
 27. The method of claim 15, wherein thepharmaceutically acceptable formulation is administered 1-5 times daily.28. The method of claim 27, wherein the pharmaceutically acceptableformulation is administered 2-3 times daily.
 29. The method of claim 28,wherein the pharmaceutically acceptable formulation is administered 3times daily.
 30. The method of claim 15, wherein 1-10 g of thepharmaceutically acceptable formulation is applied at eachadministration.
 31. The method of claim 30, wherein 1-5 g of thepharmaceutically acceptable formulation is applied at eachadministration.
 32. The method of claim 31, wherein 1-3 g of thepharmaceutically acceptable formulation is applied at eachadministration.
 33. The method of claim 32, wherein 2 g of apharmaceutically acceptable formulation is applied at eachadministration.
 34. The method of claim 33, wherein 2 g of thepharmaceutically acceptable formulation is applied topically 3 times perday.
 35. The method of claim 34, wherein the pharmaceutically acceptableformulation is a cream.
 36. The method of claim 35, wherein the cream is3VM1001.
 37. The method of claim 15, wherein the pharmaceuticallyacceptable formulation comprises copper ions disposed in a solution as aresult of leaching copper ions from a solid copper metal, and whereinthe solid copper metal consists of pure copper.
 38. The method of claim37, wherein the pharmaceutically acceptable formulation is a cream,lotion, gel or a foam.
 39. The method of claim 38, wherein thepharmaceutically acceptable formulation consists of 5%, 10%, 20%, or 30%of the solution.
 40. A method of administering the pharmaceuticallyacceptable formulation of claim 1 1-5 times daily.
 41. The method ofclaim 40 wherein the pharmaceutically acceptable formulation isadministered 2-3 times daily.
 42. The method of claim 41, wherein thepharmaceutically acceptable formulation is administered 3 times daily.43. The method of administering the pharmaceutically acceptableformulation of claim 1, wherein 1-10 g of the pharmaceuticallyacceptable formulation is applied at each administration.
 44. The methodof claim 43, wherein 1-5 g of the pharmaceutically acceptableformulation is applied at each administration.
 45. The method of claim44, wherein 1-3 g of the pharmaceutically acceptable formulation isapplied at each administration.
 46. The method of claim 45, wherein 2 gof a pharmaceutically acceptable formulation is applied at eachadministration.
 47. The method of claim 1, wherein 2 g of thepharmaceutically acceptable formulation is applied topically 3 times perday.
 48. The method of claim 47, wherein the pharmaceutically acceptableformulation is a cream.
 49. The method of claim 48, wherein the cream is3VM1001.